Abstract
1‐FROM T CELLS TO TIK TOK – DEVELOPMENTAL CONSIDERATIONS IN PEDIATRIC MILD TBI
R. Mannix1
1Boston Children's Hospital, Boston, MA, United States
Mild traumatic brain injury (mTBI), including concussion, is a common childhood injury, with as many as 20% of children sustaining an injury in the first 2 decades of life. Though there has been recent increasing awareness of the numerous ways that childhood mTBI can alter the developmental trajectory, studies specific to childhood mTBI lag behind investigations in adult populations, both in preclinical and clinical settings. As a result, there remain large gaps in the understanding of how age modifies most aspects of mTBI including genetic predisposition to worse outcome, anatomic phenotypes, secondary injury mechanisms, biomarker performance, and response to therapeutic intervention. Prioritizing pediatric mTBI research will have large public health impact but requires thoughtful and age‐appropriate translation of lessons learned in adult populations.
2‐A BIOLOGICAL BASIS FOR PERSISTENT POST‐CONCUSSION SYMPTOMS (PPCS): ENDOPHENOTYPES & BIOMARKERS
1UCLA Steve Tisch BrainSPORT Program
2UCLA Division of Pediatric Neurology, Mattel Children's Hospital
3UCLA Brain Injury Research Center, Dept of Neurosurgery
4UCLA Dept of Psychiatry
5UCLA Dept of Neurology
6UCLA Dept of Psychology
7UC Irvine, Children's Hospital of Orange County
8University of Florida, Dept of Psychology
Concussion is a biomechanically‐induced cerebral injury that results largely in functional and microstructural changes in the brain. The complex pathophysiology of acute concussive injury has been well‐described, and most of the acute changes recover with time. Clinically, concussion (or mild traumatic brain injury mTBI) represents 80‐90% of all TBI, and while most people recover, a significant subset (10‐30%) develop persistent post‐concussion symptoms (PPCS). These prolonged symptoms result in significant suffering and disability and represent a major public health issue worldwide. Increasingly, it is recognized that measurable objective biomarkers may be associated with different constellations of PPCS. The term endophenotype has been used to describe combinations of objective biomarkers with clinical phenotypes representing underlying pathophysiological changes. Autonomic, imaging, molecular and electrophysiological are all reported types of post‐TBI biomarkers. Different patients may present with different patterns of PPCS, and there is growing evidence to support distinct underlying biological endophenotypes of PPCS. These include but are not limited to autonomic dysregulation (associated with fear, anxiety, exercise intolerance), migraine (associated with headache and sensory sensitivity), inflammatory, neurovascular and neurodegeneration. This translational talk will review both preclinical and clinical evidence to support different subtypes/endophenotypes of PPCS. Identifying and characterizing these subtypes has important potential for better understanding of post‐TBI biology and recovery, and development of mechanism‐based therapeutics for PPCS.
3‐THE PUZZLE OF PERSISTING DISABILITY AFTER MILD TRAUMATIC BRAIN INJURY
L. Wilson1
1University of Stirling, Stirling, United Kingdom
Individuals with a mild traumatic brain injury (mTBI) typically report a variety of symptoms over the weeks following injury. Until recently it was thought that in most people with mTBI these symptoms resolve by three months post‐injury, and this view was supported by systematic review of the literature. A proportion were recognized as suffering from persisting symptoms, but these were believed to be a small minority. This view of outcome after mTBI is challenged by two recent large scale observational studies, TRACK‐TBI and CENTER‐TBI. Both studies recruited cases across the TBI severity range, presenting within 24 hours of injury, and with an indication for CT scanning. Analyses focussing on patients with an initial GCS of 13 to 15 in these cohorts has revealed that 50% or more report some disability (Glasgow Outcome Scale Extended <8) at 6 months, and that a similar proportion report persisting symptoms (3 or more items on the Rivermead Post‐Concussion Symptoms Questionnaire). Given the overall prevalence of mTBI, the high rates of problems reported potentially translate into a major public health issue. The findings show that we need to revise our view of what constitutes a “mild” TBI. A number of key issues concerning mTBI remain to be resolved, including increasing our knowledge of the types of problems that persist, capturing the range of pathophysiology in patients with GCS 13‐15, and understanding the potential role of pre‐injury status in the process of recovery.
4‐NEUROIMAGING AND FUNCTIONAL TESTING OF ATHLETES WITH PERSISTENT POST‐CONCUSSION SYMPTOMS
N. Marklund1
An increasing number of athletes suffer from prolonged symptoms after sports‐related concussion (SRC), and in those with persistent post‐concussive symptoms (PPCS) impaired long‐term mental health is common. In addition, dizziness and vertigo indicating vestibular dysfunction are also common complaints. We have in a series of investigations used refined neuroimaging (tau‐positron emission tomography (PET), and 7T magnetic resonance imaging (MRI)) as well as detailed neuropsychological evaluation, vestibular system testing and cerebrospinal fluid (CSF) biomarkers in cohorts of young PPCS athletes with symptom duration ≥6 months. We have observed aggregation of a tau‐PET tracer ([18F]THK5317) and a tracer for microglial activation (PK‐11195). We also performed detailed testing of the vestibular system and diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) of cerebellar white matter tracts using 7TMRI. The vestibular dysfunction was caused by an injury to the inferior vestibular nerve, not a central (cerebellar) pathology. An extensive psychometric neuropsychological test battery showed that the PPCS athletes performed significantly worse than controls. On 7TMRI, we examined 72 white matter tracts and of these, 16% of DTI and 35% of DKI metrics, in total 28%, were abnormal. CSF levels of the axonal injury marker NfL correlated with several diffusion metrics. In addition, CSF cytokine levels were also increased in PPCS athletes.
These data suggest that white matter abnormalities, perhaps in combination with an ongoing inflammation, may contribute to tau aggregation and persistent post‐concussive symptoms following sports‐related concussions.
5‐EXTRACELLULAR VESICLES FROM MESENCHYMAL STROMAL CELLS IMPROVE FUNCTIONAL AND STRUCTURAL OUTCOMES AFTER SPINAL CORD INJURY IN A RAT MODEL
S. Couillard‐Després1,2
1Institute of Experimental Neuroregeneration, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI‐TReCS), Paracelsus Medical University, Salzburg, Austria
2Austrian Cluster for Tissue Regeneration, Vienna, Austria
Local inflammation plays a pivotal role in the process of secondary damage after spinal cord injury (SCI). Limiting the extent inflammation constitutes a rational target to improve the functional outcomes after SCI. Application of mesenchymal stromal cells (MSCs) has been shown to dampen inflammation in various diseases. Modelling SCI in a rat model, we showed that in addition to MSCs, the intravenous application of extracellular vesicles (EVs) secreted by MSCs was also effective to lower the induction of inflammation. However, systemic administration of EVs is associated with delayed delivery to the site of injury and the necessity for high doses to reach therapeutic levels. We therefore scrutinized the impact of EVs injected directly into the lesion site, as compared to intravenous application, on the functional and structural outcomes after SCI.
Intralesional EVs application was superior to improve motor recovery during the first weeks post‐injury. The acute intralesional application of EVs resulted in a marked reduction of pro‐inflammatory cytokines expression and inflammatory cells accumulation in the lesion site. Furthermore, scarring and astrogliosis were more attenuated by the intralesional application of EVs. Finally, we measured that both EVs application route could preserve more white matter, as compared to the vehicle administration.
Our observation demonstrates that EVs are particularly potent when applied acutely and close to the injury. Improvement of the lesion microenvironment and the additional structural sparing could constitute valuable assets for interventions aiming for axonal regeneration or cell therapies.
6‐GLIAL CELLS IN TRAUMATIC BRAIN INJURY: GOOD FRIENDS OR ENEMIES?
L. Dimou
1Molecular and Translational Neuroscience (MTN), Ulm University, Ulm, Germany
Glial cells in the adult brain comprise most cells in the CNS, are very diverse and some of them represent stem and progenitor cells. In the CNS, microglia, astrocytes, oligodendrocytes and their progenitors, the NG2‐glia, are present and after a brain injury these are also the mediators of the brain response. My talk will focus on the reaction of glial cells to acute traumatic brain injury (TBI) and on the comparison of their response to invasive versus close head injury. We could show that TBI leads to a rapid and heterogeneous response of glial cells, not only with morphological changes but also with an increase in number and changes in their proliferation. However, the exact full functions of glial cells in the injured CNS and the mechanisms regulating their behavior are still not resolved. Furthermore, there are also various interactions between these glial cells that contribute to the pathophysiology of TBI that are still not fully understood. To tackle these questions, we used various tools such as different genetically modified mice, conditional depletion of glial cells, transcriptomic analysis as well as in vivo live imaging of these cells in the injured mouse cerebral cortex. By these techniques we were able to reveal new insights into the reaction and functional role of glia in the injured brain.
7‐TIME IS SPINE: TRANSLATIONAL UPDATE ON APPROACHES TO FACILITATE REPAIR AND REGENERATION ON THE INJURED SPINAL CORD
M. G. Fehlings
The last 10 years have witnessed significant advances in the management of acute spinal cord injury (SCI) and in translational research related to repair and regeneration of the injured spinal cord. This lecture will discuss advances in the role and timing of surgery for acute SCI and will emphasize the concept of “Time is Spine”. Areas of future direction will be discussed including the concept of “ultra‐early” surgery, duroplasty and advanced monitoring approaches. The talk will provide an update on advances in neuroprotective strategies including the sodium‐glutamate antagonist riluzole. The role of epidural stimulation of neural circuits and brain‐computer interfaces will be briefly discussed. A summary of advances in translational research regarding regenerative approaches including neural stem cells, bioengineered strategies and techniques to overcome inhibitory factors such as Rho and RGMa will be reviewed. Finally, a perspective will be provided on the current state of the art for acute SCI management and where we will be in 10 years.
8‐COMPREHENSIVE SPINAL CORD INJURY CARE
N. Weidner1
1Spinal Cord Injury Center, Heidelberg University Hospital, Heidelberg, Germany
Spinal cord injury represents a complex disease condition, which causes not just severe neurological dysfunction leading to paresis and autonomic dysfunction. Beyond this immediate impact, mid and long‐term sequels are observed, which may additionally affect well being, quality of life and functioning in activities of daily living. Therefore, research activities focus on both strategies to reverse/ameliorate the consequences of the immediate injury impact as well as long term complications. Accordingly, the presentation gives an update about a multicenter interventional study with the Nogo‐A antibody for spinal cord repair, discusses the relevance of secondary complications such as pain, heterotopic ossification and potential central nervous system alterations remote from the injury site. Finally, a first glance into the black box of outpatient care related to the degree of mobility in spinal cord injury patients will be given.
9‐SCANS: A STORY OF SHANGHAI COMA AFFERENT NERVE STIMULATION ON TRAUMATIC COMA
G. Gao
Unconsciousness at the early stage of severe traumatic brain injury is common and might be improved by right median nerve stimulation.
Our efforts initiated in 2005 when noticing a boy suffered from a car accident, fell into unconsciousness for one month, and recovered well from right median nerve stimulation intervention. The following practice of coma awakening focused on the unconsciousness in neurosurgical ICU. The positive results encouraged a random control multi centre prospective study (ACES) in China to seek high‐level evidence to help patients in coma. In this randomized controlled trial, done in 22 centres in China, participants with acute coma, at 7 to 14 days after head trauma, were randomly assigned (1:1) to either routine therapy and right median nerve stimulation (RMNS group) or routine treatment (control group). Participants and outcomes assessors were masked to group assignment. The RMNS group received 20 mA, 300 μs, 40 Hz stimulation pulses, lasting 20 s per minutes, for two weeks. The primary outcome was the rate of regaining consciousness at the 6 months after injury.
Meanwhile, we also explored the in vivo effect after right median nerve stimulation regarding biomarkers, including blood perfusion and EEG variation.
There are few effective treatments to enhance coma recovery at the early stage post‐injury. The intracranial instability and the monitoring and management operation limit the availability of invasive methods. The SCANS project may identify that the right median nerve stimulation is a safe and effective treatment for improving consciousness outcomes in traumatic coma patients.
10‐GLOBAL CHALLENGES IN NEUROTRAUMA
P. Hutchinson1,2, D. Griswold1,3, D. Clark1,4, T. Bashford1,5, B. Smith1, M. Mohan1,2, K. Budohoska1, C. Turner1, C. Whiffin1, N. Budohoska1, A. Joannides1,2, R. Trivedi1, D. Menon1, A. Kolias1,2 on behalf of the NIHR Global Health Research Group on Neurotrauma
1National Institute of Health Research Global Health Research Group on Neurotrauma, University of Cambridge, Cambridge, United Kingdom
2Neurosurgery, University of Cambridge
3University of Mississippi Medical Center, Jackson, MS, United States
4Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY, Unites States
5Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, United Kingdom
Mapping TBI care: projects including Global Neurotrauma Outcome Study (GNOS), GNOS Spine, GEOTBI Registry
Understanding TBI care: projects including ASIA‐TBI, network modeling of patient flow, Yangon Early Warning System (YEWS)
Innovation categorized across four sub‐themes (A: system refinement for cost‐effective outcomes, B: patient triage and risk stratification, C: surgical interventions, D: collection of outcomes)
Research capacity building: projects including BMJ Research to Publication, Global Neurotrauma Fellowships, Neurosurgical Publication Database
11‐TRACK‐TBI: A 10 YEAR JOURNEY TO TRANSFORM RESEARCH AND CLINICAL KNOWLEDGE IN TBI
G. Manley
In 2012, through a unique public‐private partnership, a multidisciplinary national team began enrollment of the NINDS‐funded TRACK‐TBI longitudinal, natural history study. The goal to enroll over 3000 TBI patients across the injury and age spectrum, with matched orthopedic and “friend” control subjects at 18 Level 1 trauma centers across the U.S. was exceeded. The original study has evolved into a premier clinical research network with advanced analytic cores and pipelines, capably conducting natural history, validation, device, and soon, drug trials. TRACK's 20,000+ datapoints across clinical, physiologic, neurocognitive, and behavioral, proteomic, genomic, and neuroimaging domains using the TBI Common Data Elements, and interrogation of its extensive biorepository, have resulted in actionable clinical insights, bringing evidence‐based precision to TBI's traditional diagnostic classifications and prognostic models across the injury spectrum. Regulatory advances founded on TRACK data include 2 FDA Letters of Support for TBI biomarkers, an FDA MDDT in imaging, and FDA's clearance of Abbott's i‐STAT device that assists clinicians to assess suspected mild TBI. TRACK has created a widely accessible, comprehensive TBI Information Commons, including upload of data to the FITBIR platform, to support continued TBI research. In 2022, the TRACK leadership team contributed guidance and expertise to NASEM's first‐ever TBI committee, co‐authoring its report: Accelerating Progress in Traumatic Brain Injury Research and Care which includes a clinical and research roadmap for the coming decade.
12‐PRECISION MEDICINE IN TBI: SPRINT OR MARATHON?
D. Menon1
1University of Cambridge, Cambridge, United Kingdom
The clinical challenge for neurotrauma is identify patient subsets for Precision Medicine. Unlike other complex neurological diseases, where endophenotypes (individuals with genetic predisposition to the disease) provide a route to fundamental disease biology, TBI is dominated by the effect of injury. Both genomic medicine and dissection of the molecular host response provide insights in this context, translation to clinical practice will take time. However, emerging clinical tools (especially blood biomarkers and advanced neuroimaging) allow identification of more specific pathoanatomic entities or endotypes (traumatic axonal injury, contusions, ischaemia, severe brain swelling) which have closer links to pathophysiology in “cleaner” experimental models of TBI. Identification of endotypes may provide a more rapid initial route to precision medicine – critical in three contexts. First, inadequate characterisation of some endotypes may mask true prognosis (e.g. diffuse axonal injury which only visible on MRI, but poorly visualised on CT). Second, treatment for one endotype may produce significant harm in another another (e.g. CPP augmentation can worsen vasogenic oedema). Finally, appropriate characterization could allow selection of the minority of patients who suffer from long term effects of TBI (cognitive decline and functional deterioration). Precision medicine in TBI is thus both a sprint (with refinement of management based on data provided by studies such as CENTER‐TBI and TRACK‐TBI); and a marathon (where emerging insights from molecular and genomic medicine targets and trials new therapies, and identifies subsets of patients for such interventions).
13‐THE IMPACT OF CENTER‐TBI
1Department of Neurosurgery, University Hospital Antwerp, Edegem, Belgium
2University of Cambridge, Cambridge, United Kingdom
CENTER‐TBI is a large scale collaborative project, supported by the Fp7 program of the European Union from oct 2013 to march 2021. It formed part of the InTBIR initiative, and was closely harmonized with its sister project in the US: TRACK‐TBI. CENTER‐TBI collected highly granular data in its Core obervational study on 4509 patients with TBI of all severities, and basic data on 22849 patients in its Registry. What started as a European project became a global endeavour with linked data collections in Australia, China and India, increasing the registry database to nearly 40,000 patients. It created the world's largest imaging, genetic and serum biobanks on TBI. CENTER‐TBI produced a contemporary picture of TBI in Europe, highlighting that mild TBI (mTBI: GCS 13‐15) is the commonest form of presentation and causes the greatest public health burden. “Mild” TBI is, however, not so mild and 51% of these patients had not attained full good recovery by 6 months after injury. A major focus was on comparative effectiveness analyses to identify best practices. This yielded novel insights into airway management, fluid therapy, DVT prophylaxis and surgical approaches. Extensive biomarker analyses showed that GFAP outperforms clinical decision rules in predicting the presence of CT abnormalities in patients with mTBI, but that UCH‐L1 is more informative for predicting outcome. Overall, the project has been highly productive with to date over 250 publications. The legacy data of CENTER‐TBI and its biobanks offer huge opportunities for further research and CENTER‐TBI is committed to facilitating this.
14‐CONNECTING FIELD TO FIELD: TRANSLATING RESEARCH IN TBI RELATED NEURODEGENERATION TO GAME CHANGING PRACTICE
1Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom
2Department of Neuropathology, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom
3Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
4Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Despite decades of research, we have no effective therapies for dementia. In part, this is a consequence of the disease process already being established and irreversible by the time a diagnosis is made. Attention, therefore, has turned to developing strategies to prevent or delay disease onset. Traumatic brain injury (TBI) represents one major risk factor for neurodegenerative disease (NDD), responsible for more than 3% of dementia in the community. In recent years, the relationship between TBI and NDD has attracted particular attention through increasing recognition of a specific, TBI‐associated neurodegenerative pathology, chronic traumatic encephalopathy (CTE), in former contact sports athletes, including American football and soccer, with parallel, epidemiological studies demonstrating high neurodegenerative disease risk among these populations. In theory, therefore, research in former athletes provides unique opportunities to investigate the trajectory of neurodegenerative disease from the initiating event onwards, with potential for novel intervention studies to mitigate risk. Importantly, there is also prospect that NDD risk in current and future athletes might be reduced through reduction or elimination of TBI exposure in sport.
To achieve these goals a number of multi‐center, collaborative research programs have been established to define the neuropathology of TBI‐related neurodegeneration (TReND; eg CONNECT‐TBI), establish the relationship between contact sport and lifelong health (eg FIELD) and to document mid‐life brain health outcomes in former athletes and potential risk mitigation strategies (eg BrainHOPE). In parallel, emerging research evidence generated by these various programs is informing targeted brain health initiatives and player welfare developments across multiple global sports.
15‐OPERATION BRAIN TRAUMA THERAPY AND BEYOND
P. Kochanek1
1University of Pittsburgh School of Medicine and UPMC Children's Hospital of Pittsburgh, PA, United States
Operation Brain Trauma Therapy (OBTT) is a multi‐center pre‐clinical therapy and biomarker screening consortium funded by the US Department of Defense to screen therapies and biomarkers to advance to clinical trials in severe traumatic brain injury (TBI). Three TBI models (fluid percussion injury [FPI], controlled cortical impact [CCI], and penetrating ballistic‐like brain injury [PBBI]), one at each of 3 centers, were used to test 12 therapies in >1500 rats, generating >5000 blood samples for biomarker assessments. Behavior and histology were also assessed to generate a scoring matrix. OBTT featured great rigor with treatments blinded and outcome codes broken simultaneously across centers. Two therapies showed promise, Levetiracetam and Glibenclamide (GLY). Levetiracetam generated the most points with benefit in FPI and CCI, while GLY was the second highest scoring therapy with benefit largely restricted to CCI. Serum GFAP at 24h performed best as both a prognostic and pharmacodynamic‐response biomarker, predicting therapeutic benefit. The success of GLY prompted additional pre‐clinical studies (impact of sex, assessment by MRI in CCI) and clinical studies (genetics and biomarkers assessing the SUR1/TRPM4 pathway) to optimize future precision therapy. GLY is now in a multi‐center clinical trial in contusional TBI. Additional approaches to OBTT data analysis at our sites include cross‐model comparisons, ranking by positive effects, use of machine learning and artificial intelligence to compare therapies, use of single cell RNAseq to better define therapeutic targets, and studies in a pig FPI model. Support: DAMD W81HWH‐14‐2‐0118 and W81XWH‐10‐1‐0623, NS115815, PA RFA67‐49, and the Chuck Noll Foundation.
16‐NOVEL ENDOGENOUS TARGETS TO PROMOTE NEUROPROTECTION IN TRAUMATIC SPINAL CORD INJURY
1Department of Physiology and Pathophysiology, Regenerative Medicine Program, Spinal Cord Research Centre, Children's Hospital Research Institute of Manitoba, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
Traumatic spinal cord injury (SCI) results in substantial cell death. Neurons and glia are damaged permanently at the site of injury due to primary injury. Neurodegeneration, however, progresses within the injured spinal cord through a cascade of secondary injury mechanisms that include ischemia, ionic imbalance and excitotoxicity, oxidative damage, lipid peroxidation, and glial and immune dysregulation. Thus, neuroprotective interventions are of paramount importance to attenuate permanent disruption of the spinal cord network after SCI. Given the complexity of SCI pathophysiology, therapeutic targets that can modulate several aspects of injury mechanisms are more desirable. We discovered, for the first time, that SCI induces rapid and persistent dysregulation of Neuregulin1 (Nrg1) in the spinal cord. Nrg1 is a signaling protein with diverse roles in neuronal differentiation, maturation, maintenance, axon guidance, synapse formation, and myelination in the nervous system. Our extensive in vivo and in vitro studies have uncovered a functional impact for Nrg1 dysregulation on endogenous cell responses after SCI. Increased availability of Nrg1 improves the dysregulated milieu of acute SCI by modulating glial reactivity and immune responses that can protect neurons and oligodendrocytes from inflammatory and oxidative damage. We show neuroprotective and immunomodulatory effects of transient acute Nrg1 therapy culminate in long‐term beneficial effects that results in reduced tissue degeneration, enhanced remyelination and improved functional recovery in chronic SCI. Altogether, our findings have identified an important role for Nrg1 in immune homeostasis and repair processes in the injured spinal cord, and its promise as a new relevant neuroprotective strategy for SCI.
17‐TBI NEUROIMMUNE INTERACTIONS: FROM THE BRAIN TO BODY, AND BACK AGAIN!
D. Loane1
1School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland
Traumatic brain injury (TBI) is a chronic and progressive disease, and management requires an understanding of both the primary neurological injury and the secondary sequelae that affect peripheral organs, including the respiratory system and gastrointestinal tract. Immunosuppression or chronic dysregulation within systemic immune compartments following TBI increases the host's susceptibility to subsequent infectious complications, which may also contribute to chronic neurodegenerative processes and additional long‐term neurological impairments. Here I will discuss preclinical evidence showing bidirectional interactions between the brain and systemic organs following TBI and critically assess potential underlying mechanisms.
18‐OPERATIVE SCI
B. Ishak1, W. Peul2, D. Okonkwo3, S. Saadoun4
1Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany
2University Neurosurgical Center Holland (UNCH), Leiden, Netherlands
3University of Pittsburgh, Neurosurgery, Pittsburgh, PA, United States
4Department of Neurosurgery, St. George's University of London, London, United Kingdom
Traumatic spinal cord injury (TSCI) is a devastating and debilitating condition. Along with traumatic brain injury, TSCI results in immense rates of disability, mainly affecting young men in high income countries. However, as life expectancy increases in the era of demographic change, TSCI is becoming more prevalent in the elderly. Across Europe and USA, current estimates suggest an incidence of 16 per million and 40 per million inhabitants, respectively. In terms of therapy, early intervention has been a focus of paramount importance for enhancing neurologic recovery. Pharmacological intervention in patients with TCSI remains futile, with all available drugs tested having failed to demonstrate substantial clinical benefit; with high dose methylprednisolone being associated with risks of complications and with doubtful benefit regarding neuroprotection. Unambiguously, surgical management plays a decisive role in the care of TSCI with the main objective being early decompression of the spinal cord in patients with neurological impairments as well as the restoration of spinal alignment and stability. While the concept of early surgery has been widely adopted, the timing of surgery still remains one of the most controversial aspects. Reviewing recent literature, there is increasing evidence supporting earliest possible surgery as the key tool for an improved neurological recovery after TSCI.
Central cord syndrome (CCS) is the most common type of spinal cord injury (SCI). The optimal timing of acute traumatic CCS is still a matter of debate. Early surgery (≤ 24 hours post injury) can be considered as treatment option in adult patients after traumatic CCS.
18A‐CELLS MATTER: MICROGLIA AS THE LINCHPIN FOR ACUTE AND CHRONIC POST‐TRAUMATIC DEGENERATION
D. Loane1, R. Raghupathi2, A. Helmy3, B. Semple4, J. Ojo5, O. Kokiko‐Cochran6
1School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland
2Drexel University College of Medicine, Philadelphia, PA, United States
3Department of Clinical Neuroscience, University of Cambridge, Cambridge, United Kingdom
4Department of Neuroscience, Monash University, Melbourne, Australia
5Roskamp Institute, Sarasota, FL, United States
6Department of Neuroscience & Institute for Behavioral Medicine Research, Ohio State University, Columbus, OH, United States
In the recent years, it has become clear that traumatic brain injury (TBI) is a chronic neurodegenerative disease akin to Alzheimer's and related diseases. Importantly, it affects the very young, the adult and the old. The role of inflammation mediated by the endogenous microglia has taken center stage as a common mechanism that can affect neuron survival, white matter damage and neural circuits. The co‐chairs and moderators of the symposium are experienced neuroscientist who have studied neuroinflammation in pediatric, adult and geriatric TBI. They have brought together an international cast of talented and impactful young researchers in various stages of their career from Assistant Professors (Drs. Kokiko‐Cochran, Semple and Ojo) to mid‐career faculty (Dr. Helmy). Together, the talks from these faculty will examine the intersection of age, injury and central/peripheral inflammation as it relates to chronic functional alterations and the important role that microglia play in human and experimental TBI. As we try to break down the barrier of not having any viable treatments for TBI patients, we submit that microglial associated neuroinflammation may provide a successful therapeutic target.
19‐BIOMARKERS OF TRAUMATIC BRAIN‐ AND SPINAL CORD INJURY
A. Büki1, P. Tsitsopoulos2, M. Oresic3, S. Mondello4
1Department of Neurosurgery, Örebro University, Örebro, Sweden
2Department of Neurosurgery, Hippokration General Hospital, Aristotle University School of Medicine, Thessaloniki, Greece
3School of Medical Sciences, Örebro University, Örebro, Sweden
4Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
Biomarkers of traumatic brain injury have long been investigated, yet their application in real life clinical practice is less than widespread.
Research efforts under the umbrella of InTBIR and specifically CENTER TBI provided novel results based on a bulk of data collected.
The symposium aims to provide an update on contemporary knowledge on purported clinical application of core biomarkers while also sharing novel data on emerging markers and novel technologies and approaches that may further improve our diagnostic and prognostic capabilities in the treatment of traumatic brain injury.
The session will provide a critical review and update on biomarkers of spinal cord injury.
20‐REPETITIVE MILITARY OCCUPATIONAL BLAST – STATE‐OF‐THE‐SCIENCE ON BRAIN HEALTH AND PERFORMANCE OUTCOMES ASSOCIATED WITH LOW‐LEVEL BLAST EXPOSURE
S. Turner1, S. Sloley1, W. Carr2, O. Vartanian3
1Traumatic Brain Injury Center of Excellence, Defense Health Agency, Silver Spring, MD, United States
2Walter Reed Army Institute of Research, Silver Spring, MD, United States
3Defence Research and Development Canada, Toronto, Ontario, Canada
Unlike the recent conflicts in Afghanistan and Iraq where combat‐related, high‐level blast exposures (e.g., improvised explosive devices) were prevalent and associated with traumatic brain injuries and other polytrauma, current exposures among United States military Service members (SMs) are commonly low‐level associated with occupational heavy weapons training in training. Given this shift in military operations, the United States Congress and Department of Defense have specified the need for conducting medical research on this occupational (low‐level) blast exposure among Armed Forces members who train with high‐overpressure weapon systems (e.g., shoulder mounted, .50 Cal, indirect fires, and explosive breaching). In response, specific research inquiries include: characterization and methods for capturing chronic exposure to occupational blast, to include those military occupational specialties considered to be at high risk for exposure; quantification of the association between acute low‐level blast exposure and acute alterations on brain health and performance; and potential preventative efforts for adverse outcomes associated with acute and chronic blast exposure. In this session, presentations will convey a brief, high‐level overview of the state of the science in this field, followed by in‐depth descriptions of original/new findings from field and clinical research studies probing the acute and chronic brain health outcomes related to occupational blast exposure. The session ends with a presentation on the development of policy based on research findings, and an open question and answer and/or discussion with the panelists.
21‐BRAIN INJURY IN INTIMATE PARTNER VIOLENCE
S. Shultz1, K. Mason2, P. van Donkelaar2, C. Esopenko3, J. Lifshitz4, E. Valera5
1Monash University, Melbourne, Australia
2University of British Columbia – Okanagan, Kelowna, BC, Canada
3Rutgers University, Newark, NY, United States
4University of Arizona, Phoenix, AZ, United States
5Harvard University, Cambridge, MA, United States
Approximately 1/3 of adult women have experienced intimate partner violence (IPV), and the prevalence, severity, and frequency of IPV has been exacerbated during COVID‐19 and the related lockdowns. Among the many challenges faced by IPV survivors, the physical assaults result in brain injury in the large majority of IPV survivors. Yet the nature of this brain damage and how it contributes to function has been remarkably understudied. Mild traumatic brain injury (mTBI) is common in the general population and repetitive mTBI is gaining specific recognition. Survivors of IPV typically do not seek medical attention and may suffer subsequent mTBIs in the midst of recovery. It cannot be assumed that mTBI from IPV is equivocal to those that have been studied in athletics and the military in terms of debilitating and persisting neurological issues. Unique aspects of mTBI in IPV survivors include being highly repetitive and often coupled with other injuries, involving strangulation‐related trauma and elevated risk during pregnancy, and critically, typically remaining untreated in the acute setting. The poor understanding of the consequences and burden of brain injury in IPV is a major knowledge gap that is imperative to address if we are to improve the care and outcomes for IPV survivors. The proposed symposium, which consists of a diverse and balanced group of junior and senior scientists, will feature recent findings from clinical and preclinical studies that provide insight into the epidemiology, functional and pathological consequences, biomarkers, and treatments of IPV‐related brain injury.
22‐THE BRAIN EXPOSED TO REPITITIVE HEAD IMPACTS ‐ EFFECTS ACROSS THE LIFE SPAN
I. Koerte1, W. Stewart2, E. Russell2, M. Alosco3, E. Bonke1
1Ludwig‐Maximilians‐University, Munich, Germany
2Queen Elizabeth University Hospital, Glasgow, United Kingdom
3Boston University, Boston, MA, United States
Millions of athletes around the globe are exposed to repetitive head impacts while participating in contact or collision sport. While an increased risk of neurodegenerative disease associated with exposure to repetitive head impacts had long been presumed, the pathophysiology driving this outcome remained incompletely understood. Recent research, however, has significantly expanded our knowledge of the effects of repetitive head impacts on the brain. Studies performed over the past 5 years have explored the consequences of exposure to repetitive head impacts, including lifelong brain health consequences, through focusing on three important periods across the life span of the athlete: 1. Large‐scale epidemiological studies have revealed an increased risk of neurodegenerative disorders in deceased elite athletes compared to non‐exposed populations; 2. Comprehensive prospective studies in former competitive athletes exposed to repetitive head impacts have characterized clinical presentations in the living that include cognitive decline and psychiatric symptoms; 3. Prospective interdisciplinary studies in youth athletes at the beginning of exposure to repetitive head impacts have identified early signs of alterations in brain development.
23‐SPREADING DEPOLARIZATION IN ACUTE CEREBRAL INJURIES
J. Dreier1, A. Friedman2, B. Balanca3
1Charité Universitätsmedizin Berlin, Berlin, Germany
2Dalhousie University, Halifax, NS, Canada
3University of Lyon, Lyon, France
In brain gray matter, neuronal cytotoxic edema and magnetic resonance imaging (MRI) diffusion restriction are morphological correlates of the potentially reversible electrophysiological phenomenon known as spreading depolarization (SD). Neurons die if depolarization and cytotoxic edema persist, as determined by a negative ultraslow potential (NUP) in electrophysiology and continued diffusion restriction in MRI. Distinct but merging segments of the SD continuum from short‐duration waves to intermediate‐duration waves to terminal waves occur in a variety of clinical conditions, including migraine aura, transitory ischemic attacks, ischemic stroke, traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (aSAH) and delayed cerebral ischemia, spontaneous intracerebral hemorrhage, subdural hematoma, development of brain death, and the dying process during cardiocirculatory arrest. In a recent prospective, observational, multicenter cohort study in 138 TBI patients, the occurrence of SD clusters was independently associated with poor outcome. In DISCHARGE‐1, a recent prospective, observational, multicenter, cohort, phase III diagnostic trial in 180 aSAH patients, SD variables were included in each multiple regression model for longitudinal neuroimaging‐proven early, delayed, and total brain damage, outcome at seven months, and patient death. These statistical results strongly suggest that SDs are an independent real‐time biomarker of progressive brain injury, although short‐lasting SDs can be harmless. We will discuss these recent clinical trials. SD is also a promising but complicated target for therapeutic intervention. Meaningful animal experimental models are essential to develop novel therapies. Therefore, we will also discuss animal approaches to the study of TBI and the role of SDs in these models.
24‐POST‐TRAUMATIC EPILEPSY (PTE): A LONG‐TERM COMPLICATION OF TRAUMATIC BRAIN INJURY; TRANSLATIONAL AND CLINICAL STUDIES IDENTIFYING DIAGNOSTIC AND PROGNOSTIC BIOMARKERS
P. Vespa1, A. Galanopoulou2, D. Agoston3, D. Duncyn4
1UCLA, Los Angeles, CA, United States
2Albert Einstein College of Medicine, Bronx, NY, United States
3Uniformed Services University of the Health Sciences, Bethesda, MD, United States
4University of Southern California, Los Angeles, CA, United States
Post‐traumatic epilepsy (PTE) is a common but poorly understood long‐term outcome of traumatic brain injury (TBI). The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is a large, NIH funded international, Center without Walls (CWOW) research program working on PTE with the objectives of developing the techniques, biomarkers and to identify patient populations necessary to carry out future cost effective full‐scale clinical trials of PTE prevention therapies.
The Symposium will present EEG, imaging and blood‐based biomarker data identified in preclinical and clinical studies, will discuss opportunities and challenges of harmonizing preclinical and clinical multimodality data to create a centralized data archive for the research community.
25‐GENETIC BACKGROUND DETERMINES THE EFFICACY OF ANESTHETIC PRECONDITIONING IN A
DROSOPHILA MELANOGASTER (FRUIT FLY)
MODEL OF POLYTRAUMA WITH TRAUMATIC BRAIN INJURY (TBI)
1University of Wisconsin‐Madison, Medical Genetics, Madison, WI, United States
The interpretation of virtually all animal studies of traumatic brain injury (TBI) are compromised by background exposure to anesthetics which have tissue‐protective effects. Since cellular responses to damage are similar across tissues and evolutionarily conserved, we developed a Drosophila melanogaster (fruit fly) model of blunt TBI (1). Using this model, we discovered that exposure of flies to the VGAs isoflurane (ISO) and sevoflurane (SEVO) prior to TBI substantially reduces early mortality and extends lifespan (2).
To test the hypothesis that the efficacy of AP is determined by genetic factors, we subjected different Drosophila strains to TBI with or without AP with ISO and compared mortality at 24 h after TBI. The experiments adhere to applicable ARRIVE (Animal Research: Reporting of In Vivo Experiments) reporting guidelines (preclinical animal research). Approval from the IACUC has been waived. TBI was induced using a High‐Impact Trauma (HIT) device (1), anesthesia was administered using the Serial Anesthesia Array (SAA) (3) as described previously.
We found that the efficacy of AP to TBI in Drosophila is largely determined by genetic background. Our findings are significant because they demonstrate that preconditioning with VGAs (i) suppresses mortality after TBI and (ii) that pharmacogenetic factors determine the efficacy of AP with ISO. These factors are disregarded in most animal models of TBI and may contribute to the difficulty in translating pharmacologic brain protecting strategies into clinical practice.
References: (1) R. Katzenberger et al. PNAS 2013; (2) J. Fischer et al. AnesthAnalg 2018; (3) Z. Olufs et al. Sci.Rep. 2018
26‐CYTOTOXIC BRAIN EDEMA IS ASSOCIATED WITH NEUROINFLAMMATION AND RETRACTION OF PERIVASCULAR AQUAPORIN‐4 FOLLOWING EXPERIMENTAL SEVERE TRAUMATIC BRAIN INJURY – A MULTI‐MODAL IMAGING STUDY
1Karolinska University Hospital, Clinical Neuroscience, Stockholm, Sweden
2Karolinska University Hospital, Neuroscience, Stockholm, Sweden
3Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, Australia
4Arizona State University, Barrow Neurological Institute at Phoenix Children's Hospital and Department of Child Health, Phoenix, AZ, United States
5Karolinska University Hospital, Karolinska Experimental Research and Imaging Center, Stockholm, Sweden
27‐MUSIC AS A NOVEL AND NON‐INVASIVE REHABILITATIVE PARADIGM TO PROMOTE MOTOR, AFFECT, AND COGNITIVE RECOVERY AFTER EXPERIMENTAL TRAUMATIC BRAIN INJURY
1University of Pittsburgh, Neuroscience, Pittsburgh, PA, United States
2University of Pittsburgh, Safar Center for Resuscitation Research, Pittsburgh, PA, United States
3Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, United States
4University of Pittsburgh, Pediatric Critical Care Medicine, Pittsburgh, PA, United States
28‐INTERLEUKIN‐13 AND ITS RECEPTOR ARE SYNAPTIC PROTEINS INVOLVED IN PLASTICITY AND NEUROPROTECTION
1Ulm University Clinic, Neurology, Ulm, Germany
29‐MULTI‐COMPARTMENTAL METABOLIC DYNAMICS FOLLOWING SEVERE TRAUMATIC BRAIN INJURY HIGHLIGHT THE NECESSITY OF FOCAL MONITORING
1Karolinska University Hospital, Clinical Neuroscience, Stockholm, Sweden
2Karolinska University Hospital, Department of Physiology and Pharmacology, Stockholm, Sweden
3Karolinska University Hospital, Department of Section for Perioperative Medicine and Intensive Care, Stockholm, Sweden
4Karolinska University Hospital, Neurosurgery, Stockholm, Sweden
30‐CONTINUOUS PHARMACOLOGICAL DATA EXTRACTION THROUGH COMPUTER VISION: IMPROVING CONTINUOUS TREATMENT DATA COLLECTION IN TBI
1University of Manitoba, Biomedical Engineering, Winnipeg, MB, Canada
2University of Manitoba, Surgery, Winnipeg, MB, Canada
3University of Manitoba, Department of Human Anatomy and Cell Science, Winnipeg, MB, Canada
4University of Manitoba, Centre on Aging, Winnipeg, MB, Canada
5Cambridge University, Department of Medicine, Cambridge, United Kingdom
31‐SPINAL CORD INJURY‐DERIVED MONOCYTES ALTER THE VIABILITY AND IMMUNOMODULATORY PHENOTYPE OF NEURAL CREST‐DERIVED DENTAL PULP STEM
1South Australian Health and Medical Research Institute, Neil Sachse Centre for Spinal Cord Research, Lifelong Health Theme, Adelaide, Australia
2University of Adelaide, Adelaide Medical School, Faculty of Health and Medical Sciences, Adelaide, Australia
3University of Adelaide, School of Biomedicine, Adelaide, Australia
4South Australian Health and Medical Research Institute, Adelaide Health and Biomedical Precinct Cytometry, Adelaide, Australia
5South Australian Health and Medical Research Institute, Neuropsychiatric Laboratory, Lifelong Health Theme, Adelaide, Australia
6Royal Adelaide Hospital, Spinal Services, Adelaide, Australia
7University of Adelaide, Centre for Orthopaedic and Trauma Research, Adelaide, Australia
8University of Adelaide, Mesenchymal Stem Cell Laboratory, School of Biomedicine, Adelaide, Australia
9South Australian Health and Medical Research Institute, Precision Medicine Theme, Adelaide, Australia
Neural crest derived dental pulp stem cells (DPSC) show superior regeneration and immunomodulation after injury, but display poor survival under the severe inflammatory conditions of acute spinal cord injury (SCI). Our study aimed to understand the impact of inflammatory mediators on stem cell viability. Moreover, a novel ex vivo approach of pre‐conditioning DPSC with peripheral blood monocytes (Mο) from SCI animals was developed to strengthen immunomodulation and viability for future engraftment.
Mο were isolated from SCI or laminectomy‐only (Sham) Sprague Dawley rats three days post‐injury using density gradient centrifugation and fluorescence activated cell sorting (FACS). hDPSC were co‐cultured with Mο with or without inflammatory cytokine stimulation (TNF‐α; TNF‐α + IFN‐γ) for a further three days ex vivo. Lactate dehydrogenase assays evaluated cell viability and cytometric bead arrays analysed regulatory protein (V‐CAM‐1, I‐CAM‐1) and inflammatory cytokine release (IL‐6).
Cytotoxicity analysis revealed that hDPSC pre‐conditioning with Mο and inflammatory cytokines improved stem cell viability compared to hDPSC monoculture. TNF‐α or synergistic TNF‐α + IFNγ stimulation increased V‐CAM‐1 and I‐CAM‐1 secretion. Interestingly, hDPSC secreted significantly more IL‐6 following pre‐conditioning with SCI‐Mο than with Sham‐Mο. FACS analysis of SCI‐Mο and Sham‐Mο uncovered differential CD11b, CD43, SIRPa and MHCII expression.
Our hDPSC pre‐conditioning strategy demonstrates a novel role for SCI‐derived Mο populations in regenerative medicine. We have shown that pre‐conditioning hDPSC with peripheral blood Mο following SCI may be an effective tool to enhance their anti‐inflammatory and immunomodulatory properties. The findings indicate that allogeneic and autologous monocyte‐stem cell preconditioning protocols warrant further investigation.
32‐HIGHER LEVELS OF NEUROFILAMENT LIGHT ASSOCIATED WITH PSYCHOMOTOR FUNCTION IN YOUTH SOCCER PLAYERS – A REPIMPACT STUDY
1Ludwig‐Maximilians University, Munich, Germany
2NICUM (NeuroImaging Core Unit Munich), Munich, Germany
3Brigham and Women's Hospital, Boston, MA, United States
4Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia
5Ludwig‐Maximilians University, Munich, Germany
6Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Augsburg, Augsburg, Germany
7Oslo Sports Trauma Research Center, Department of Sports Medicine, Norwegian School of Sport Sciences, Oslo, Norway
8University Hospital, Division of Mental Health and Addiction, Oslo, Norway
9University Hospital KU Leuven, Leuven, Belgium
10PROVIDI Lab, Image Sciences Institute, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
11Ludwig‐Maximilians University, Munich, Germany
12Ludwig‐Maximilians University, Munich, Germany
13Department of Mathematics, Tel‐Aviv University, Tel‐Aviv, Israel
14Brigham and Women's Hospital, Boston, MA, United States
15Harvard Medical School, Boston, MA, United States
16Boston University, Boston, MA, United States
17Boston University, Boston, MA, United States
18Harvard Medical School, Boston, MA, United States
33‐MYELINATION IS ASSOCIATED WITH LESS TAU SPREADING IN INDIVIDUALS AT RISK FOR CHRONIC TRAUMATIC ENCEPHALOPATHY
1Harvard Medical School, Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, United States
2Ludwig‐Maximilians‐Universität, cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, University Hospital, Munich, Germany
3NICUM (NeuroImaging Core Unit Munich), Munich, Germany
4Ludwig‐Maximilians‐Universität LMU, Institute for Stroke and Dementia Research, Klinikum der Universität München, Munich, Germany
5Boston University School of Public Health, Department of Biostatistics, Boston, MA, United States
6The University of Melbourne and Melbourne Health, Melbourne Neuropsychiatry Centre, Department of Psychiatry, Carlton South, VIC, Australia
7Boston University School of Medicine, Alzheimer's Disease and CTE Center, Boston, MA, United States
8Banner Alzheimer's Institute, Phoenix, Arizona, United States
9Harvard Medical School, Center for Clinical Spectroscopy, Department of Radiology, Brigham and Women's Hospital, Boston, MA, United States
10Harvard Medical School, Department of Radiology, Brigham and Women's Hospital, Boston, MA, United States
11German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
12University of Nevada School of Integrated Health Sciences, Chambers‐Grundy Center for Transformative Neuroscience, Department of Brain Health, Nevada, United States
13Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States
14University School of Medicine, Departments of Neurology, Neurosurgery, and Anatomy & Neurobiology, Boston, MA, United States
15Harvard Medical School, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States
16Ludwig‐Maximilians‐Universität, Graduate School of Systemic Neurosciences, Munich, Germany
34‐POST‐INJURY ALCOHOL USE IS ASSOCIATED WITH PROLONGED RECOVERY AFTER CONCUSSION IN NCAA ATHLETES
1University of Washington, Seattle, WA, United States
2University of California, Los Angeles, Los Angeles, CA, United States
3University of Michigan, Ann Arbor, MI, United States
4Medical College of Wisconsin, Milwaukee, WI, United States
5Indiana University, Indianapolis, IN, United States
35‐BLOOD BIOMARKERS PREDICT RADIOGRAPHIC AND CLINICAL OUTCOMES IN PEDIATRIC TRAUMATIC BRAIN INJURY: AN ANALYSIS OF 519 CHILDREN
1Emory University, Neurosurgery, Atlanta, GA, United States
2Emory University, Emergency Medicine, Atlanta, GA, United States
3Children's Healthcare of Atlanta, Neurosurgery, Atlanta, GA, United States
4Emory University, Neuropsychology, Atlanta, GA, United States
36‐PRE‐INTERVENTION BLOOD HYPERPHOSPHORYLATED TAU AND UBIQUITIN C‐TERMINAL HYDROLASE‐L1 CONCENTRATIONS ARE ASSOCIATED WITH MAGNITUDE OF SYMPTOM IMPROVEMENT FOLLOWING TARGETED INTERVENTION IN PATIENTS WITH CHRONIC TRAUMATIC BRAIN INJURY
1University of Pittsburgh, Neurosurgery, Pittsburgh, PA, United States
2University of Pittsburgh Medical Center, Pittsburgh, PA, United States
3University of Pittsburgh, Orthopedic Surgery, Pittsburgh, PA, United States
4University of Pittsburgh, Pittsburgh, PA, United States
5Uniformed Services University, Bethesda, MD, United States
37‐CHIMERA TRAUMATIC BRAIN INJURY IN A MOUSE MODEL OF TAUOPATHY
1University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, BC, Canada
2University of British Columbia, Departments of Mechanical Engineering and Orthopaedics, Vancouver, BC, Canada
3University of British Columbia, International Collaboration on Repair Discoveries, Vancouver, BC, Canada
4Simon Fraser University, Department of Chemistry, Burnaby, Canada
38‐SINGLE‐CELL ATLAS ACROSS THREE MURINE TBI MODELS YIELDS HETEROGENEOUS TRANSCRIPTOME BASED ON SEVERITY, SEX, CORTICAL REGION, AND CELL‐SUBTYPE ‐ IDENTIFYING NOVEL POTENTIAL BIOMARKERS AND TARGETS
1Barrow Neurological Institute at Phoenix Children's Hospital, Neurology, Neurosurgery, Neurobiology, Phoenix, AZ, United States
2University of Pittsburgh, Pittsburgh, PA, United States
3Massachusetts General Hospital, Boston, MA, United States
4Barrow Neurological Institute at Phoenix Children's Hospital, Neurosurgery, Phoenix, AZ, United States
5Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, United States
39‐EXPERIMENTAL SPINAL CORD INJURY REVEALS NOVEL HETEROGENIC MONOCYTE SUBPOPULATIONS IN PERIPHERAL BLOOD
1University of Adelaide, School of Biomedicine, Adelaide, Australia
2South Australian Health and Medical Research Institute, Neil Sachse Centre for Spinal Cord Research, Lifelong Health Theme, Adelaide, Australia
3Royal Adelaide Hospital, Spinal Services, Adelaide, Australia
4University of Adelaide, Centre for Orthopaedic and Trauma Research, Adelaide, Australia
5University of Adelaide, School of Biomedicine, Mesenchymal Stem Cell Laboratory, Adelaide, Australia
6South Australian Health and Medical Research Institute, Precision Medicine Theme, Adelaide, Australia
7South Australian Health and Medical Research Institute, Adelaide Health and Biomedical Precinct Cytometry, Adelaide, Australia
8South Australian Health and Medical Research Institute, Neuropsychiatric Laboratory, Lifelong Health Theme, Adelaide, Australia
9University of Adelaide, Adelaide Medical School, Adelaide, Australia
The inflammatory cascade after spinal cord injury (SCI) is a major outcome measure of many preclinical and clinical studies. However, measuring intraspinal inflammation is not possible antemortem and can be challenging or invasive in animal models and human trials. Therefore, a need remains for efficient and ethical analysis of prognostic immunological biomarkers that can be adopted into acute clinical investigation.
A flow cytometry protocol was developed to characterise the peripheral blood cellular immune response 1‐28 days post‐injury. Female adult (200‐300g) Sprague‐Dawley rats received moderate T10 contusion (200kDyne) injuries or laminectomies (Sham), and peripheral blood mononuclear cells (PBMCs) were obtained after whole blood extraction. Fluorescence activated cell sorting (FACS) utilising a novel 11‐parameter panel that allows for rapid processing through simultaneous staining characterised the individual responses of B cells, T cells, NK cells and monocytes, and RT‐qPCR was used to measure inflammatory polarisation.
PBMC phenotypic proportions varied significantly between groups and post‐injury timepoints. Intriguingly, FACS analysis revealed the presence of four novel monocyte subpopulations based on differential CD11b and CD43 expression, confirmed by additional surface marker expression. The panel also identified the presence of additional cell populations, including plasmacytoid dendritic cells at 28 days post‐SCI.
Peripheral blood may be used as an efficient means of analysing inflammatory biomarkers after SCI, encouraging further work on utility for injury prognostication. Furthermore, monocyte subpopulation heterogeneity highlights the complexity of the cellular immune response after SCI and emphasizes the need for complete inflammatory characterisation to better understand peripheral immune contributions to injury progression.
40‐CHARACTERIZING A MURINE MODEL TO DIAGNOSE AND STUDY CONCOMITANT SPINAL CORD AND BRAIN INJURIES: DO CO‐OCCURRING INJURIES AFFECT DEFICITS?
1University of British Columbia, International Collaboration on Repair Discoveries, Vancouver, BC, Canada
2University of British Columbia, Vancouver, BC, Canada
41‐AN IMPLANTED SPINAL WINDOW CHAMBER ALLOWS FOR CHRONIC LONGITUDINAL
IN VIVO
MICROSCOPY FOLLOWING EXPERIMENTAL SPINAL CORD INJURY IN THE MOUSE.
1Charité, Neurosurgery, Berlin, Germany
2Charité, Research Workshop at the Charité, Berlin, Germany
3Charité, Experimental Neurology, Berlin, Germany
4Toronto Western Hospital, University Health Network, Neurosurgery, Toronto, ON, Canada
42‐DIGESTION OF CHONDROITIN SULPHATE PROTEOGLYCANS BY AAV5‐ADAMTS4 GENE THERAPY ENHANCES NON‐NEURONAL RESPONSES TO CONTUSIVE SPINAL INJURY
1University of Auckland, Anatomy and Medical Imaging, Auckland, New Zealand
2University of Auckland, Centre for Brain Research, Auckland, New Zealand
3University of Auckland, Pharmacology and Clinical Pharmacology, Auckland, New Zealand
43‐USING MAGNETIC RESONANCE IMAGING (MRI) AND BIG DATA MACHINE LEARNING TO DETECT STRUCTURAL DAMAGE IN PATIENTS WITH CONCUSSION
1TBIFinder inc., Hamilton, Canada
2McMaster University, 2Department of Electrical and Computer Engineering, Hamilton, Canada
3St. Joseph's Healthcare Hamilton, Imaging Research Centre, Hamilton, Canada
4University of Toronto, Department of Physical Medicine & Rehabilitation, Toronto, Canada
5Toronto Rehabilitation Institute, Toronto, Canada
6neurorad.ch, Zurich, Switzerland
7University hospital of Schleswig‐Holstein, Department of Radiology and Neuroradiology, Kiel, Germany
8McMaster University, School of Biomedical Engineering, Hamilton, Canada
9McMaster University, Department of Radiology, Hamilton, Canada
44‐ARE MILD TRAUMATIC BRAIN INJURY AND CONCUSSION SEPARATE ENTITIES? A PILOT STUDY USING FMRI
1McGill University, Montréal, QC, Canada
Mild traumatic brain injury (mTBI) and concussion are used synonymously, however differences in their operational definitions create diagnostic controversies. With the concussion definition1, developed in the sports context, patients need not have the objective clinical signs (e.g., loss of consciousness), but instead only post‐concussive symptoms (PCS), whereas all are essential for the mTBI definition.2
We aimed to clarify these injury definitions by comparing functional magnetic resonance imaging (fMRI) activations between individuals fitting the mTBI definition2 and those fitting the concussion definition1 without the mTBI criteria.
Blood‐oxygen‐level‐dependent (BOLD) signal changes associated with a working memory task3 were compared from symptomatic mTBI and concussion patients, and matched controls. We obtained average percent signal change from baseline to working memory condition for each region of interest.
Preliminary analysis of BOLD signal changes within regions of interest show differences in task‐related BOLD responses between the mTBI and concussion groups.
These results suggest that we may need to treat mTBI and concussion as distinct diagnostic entities, with the goal of more accurate diagnoses across disciplines.
McCrory P, Meeuwisse W, Dvořák J, et al. Consensus statement on concussion in sport—the 5th international conference on concussion in sport held in Berlin. British Journal of Sports Medicine. 2017;51(11):838‐847 Holm L, Cassidy JD, Carroll LJ, Borg J. Summary of the WHO Collaborating Centre for Neurotrauma Task Force on Mild Traumatic Brain Injury. Journal of Rehabilitation Medicine. 2005;37(3):137‐141
Petrides M. Frontal lobes and memory. Handbook of Neuropsychology. Vol 2. Elsevier, New York; 2000:67‐84
45‐AN OPEN‐ACCESS DATA SET TO INVESTIGATE THE EFFECTS OF REPETITIVE SUB‐CONCUSSIVE HEAD IMPACTS IN SPORTS ON BRAIN MICROSTRUCTURE
1University Hospital RWTH Aachen, Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, Aachen, Germany
2Research Centre Juelich, Neuroscience, Juelich, Germany
3University Hospital RWTH Aachen, Department of Neurology, Medical Faculty, Aachen, Germany
4University Hospital RWTH Aachen, JARA‐BRAIN Institute Molecular Neuroscience and Neuroimaging, Aachen, Germany
Sub‐concussive head impacts are frequently experienced by athletes practicing different contact and collision sports. While ‐by definition‐ these impacts come without apparent signs and symptoms of a concussion, findings from recent studies suggest cumulative changes in the brain when athletes are exposed to these impacts repetitively over time. Results from diffusion MRI studies examining these changes are mixed and generally underpowered.
46‐REDUCED SPEAKING RATE IN PERSONS WITH TRAUMATIC BRAIN INJURY IS INDUCED BY UNDERLYING COGNITIVE IMPAIRMENT: EVIDENCE FROM DIFFERENTIAL IMPACT OF TASK DEMANDS
1Brigham and Women's Hospital, Psychiatry, Boston, MA, United States
2MGH Institute of Health Professions, Communication Sciences and Disorders, Boston, MA, United States
3University of São Paulo, Neurology, São Paulo, Brazil
4Hospital das Clinicas, Neurology, São Paulo, Brazil
This study aimed to (1)determine the effect of cognition and oromotor capacity on the speaking rate in individuals with TBI, and (2)compare the speaking rate of individuals with TBI to cognitively‐normal individuals during tasks with different cognitive demands.
47‐CORTICAL REORGANIZATION AFTER TRAUMATIC BRAIN INJURY PREDICTS VERBAL FLUENCY OUTCOMES
1Brigham and Women's Hospital, Psychiatry, Boston, MA, United States
2University of São Paulo, Radiology, São Paulo, Brazil
3University of Texas Southwestern Medical Center, Dallas, TX, United States
4University of São Paulo, Neurology, São Paulo, Brazil
One‐third of individuals with diffuse axonal injury (DAI) have impaired motor function due to muscle spasticity, which results in communication impairment. The relationship between brain damage and neurological mechanisms supporting communication recovery following DAI has remained mostly unknown. Objective: Analyze cortical thickness changes over time (indexed by deltaMRI) as a predictor of verbal fluency outcomes (indexed by deltaVF scores) in DAI.
48‐ASSOCIATION OF INITIAL TRAUMA CHARACTERISTICS IN SEVERE TRAUMATIC BRAIN INJURY WITH LONG TERM CLINICAL OUTCOMES AND MARKERS OF NEURODEGENERATION AND NEUROINFLAMMATION – A PILOT STUDY
1Karolinska University Hospital, Department of Neurology, Stockholm, Sweden
2Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden
3University of Manitoba, Section of Neurosurgery, Department of Surgery, Rady Faculty of Health Sciences, Winnipeg, Canada
4Karolinska University Hospital, Department of Radiology, Stockholm, Sweden
49‐MAST TRIALS ‐ STRENGTHENING THE EVIDENCE BEHIND THE USE OF ANTIEPILEPTIC DRUGS IN TBI PATIENTS
1Cambridge University, Neurosurgery, Cambridge, United Kingdom
2Cambridge University Hospital, Cambridge, United Kingdom
The incidence of early PTS following severe TBI is as high as 14% and their prevention can limit impairments in brain autoregulation, and may prevent development of late PTS. There is no high‐quality evidence regarding the optimal duration of treatment for patients started on an AED for acute PTS or regarding their prevention(2).
References
Frey LC. Epidemiology of Posttraumatic Epilepsy: A Critical Review. Epilepsia. 2003; 44:11 17.
Brain Trauma Foundation Guidelines 4th Edition. 2016
50‐GLOBAL CONSENSUS‐BASED REGISTRY FOR TRAUMATIC BRAIN INJURY ‐ GEO‐TBI
1Cambridge University, Neuroscience, Cambridge, United Kingdom
51‐BRAIN BIOCHEMICAL ALTERATIONS ASSOCIATED WITH COGNITIVE FUNCTION IN YOUTH SOCCER PLAYERS – A REPIMPACT STUDY
1Ludwig‐Maximilians University, Munich, Germany
2NICUM (NeuroImaging Core Unit Munich, Munich, Germany
3Brigham and Women's Hospital, Boston, MA, United States
4Ludwig‐Maximilians University, Munich, Germany
5Boston University, Boston, MA, United States
6BrainSpec, Boston, MA, United States
7Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Augsburg, Augsburg, Germany
8Oslo Sports Trauma Research Center, Department of Sports Medicine, Norwegian School of Sport Sciences, Oslo, Norway
9Oslo University Hospital, Division of Mental Health and Addiction, Oslo, Norway
10PROVIDI Lab, Image Sciences Institute, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
11University Hospital KU Leuven, Leuven, Belgium
12Ludwig‐Maximilians University, Munich, Germany
13Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia
14Ludwig‐Maximilians University, Munich, Germany
15Department of Mathematics, Tel‐Aviv University, Tel‐Aviv, Israel
16Boston University, Boston, MA, United States
17Brigham and Women's Hospital, Boston, MA, United States
18Harvard Medical School, Boston, MA, United States
19Harvard Medical School, Boston, MA, United States
52‐VOLUMETRIC BRAIN CHANGES IN CORTICAL AND SUBCORTICAL REGIONS OF FORMER AMERICAN FOOTBALL PLAYERS YEARS AFTER EXPOSURE TO REPETITIVE HEAD IMPACTS
1Brigham and Women's Hospital, Psychiatry, Boston, MA, United States
2Boston University, Department of Biostatistics, Boston, MA, Germany
3Boston University, Boston University Alzheimer's Disease Research Center and CTE Center, Department of Neurology, Boston, MA, United States
4Ludwig‐Maximilians University, Department of Child and Adolescent Psychiatry, Munich, Germany
5Ludwig‐Maximilians University, Graduate School of Systemic Neurosciences, Munich, Germany
6Harvard Medical School, Psychiatry, Boston, MA, United States
7Brigham and Women's Hospital, Department of Radiology, Boston, MA, United States
8University of Nevada Las Vegas, Chambers‐Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, Las Vegas, NV, United States
9Arizona State University, Translational Genomics Research Institute, and Arizona Alzheimer's Consortium, Phoenix, AZ, United States
10Boston University, Department of Anatomy & Neurobiology, Boston, MA, United States
11Boston University, Neurosurgery, Boston, MA, United States
53‐PRE‐INJURY SLEEP AS A MODERATOR OF COGNITIVE FUNCTIONING IN CHILDREN AND ADOLESCENTS WITH MILD TRAUMATIC BRAIN INJURY ACROSS THE FIRST 6 MONTHS POST‐INJURY
1University of Calgary, Psychology, Calgary, AB, Canada
2Case Western Reserve University, Cleveland, OH, United States
3Rainbow Children's Hospital, Cleveland, OH, United States
4Brigham Young University, Provo, UT, United States
5Nationwide Children's Hospital, Columbus, OH, United States
6University Hospitals Health System, Cleveland, OH, United States
7Hotchkiss Brain Institute, Calgary, AB, Canada
8Alberta Children's Hospital Research Institute, Calgary, AB, Canada
54‐TRAUMATIC BRAIN INJURY IN ELDERLY PATIENTS WITH PRE‐INJURY ANTITHROMBOTIC TREATMENT: A RETROSPECTIVE STUDY
1University Hospital KU Leuven, Biomechanics Section, Leuven, Belgium
2University Hospital KU Leuven, Neurosurgery, Leuven, Belgium
The incidence of acute subdural hematomas was 44.8% in the VKA group, 27.2% in the acetylsalicylic acid group, 30.9% in the group with abnormal tests but without anti‐thrombotics and 26.3% in the reference group (p < 0.01).
30 day mortality rates in the same groups were 22.4%,11.3%, 18.7% and 10.0% respectively (p < 0.01). Acetylsalicylic acid intake did not result in any change in hemorrhage rate nor outcome with respect to the reference group. Both hemorrhage rate and outcome were worse in the VKA group, but the group with abnormal coagulation tests without antithrombotic treatment was in between.
55‐INCREASING THE EFFICIENCY OF CEREBROVASCULAR AUTOREGULATION‐GUIDED NEUROPROTECTION FOR TRAUMATIC BRAIN INJURY PATIENTS
1Kaunas University of Technology, Health Telematics Science Institute, Kaunas, Lithuania
2Lithuanian University of Health Sciences, Department of Intensive Care, Academy of Medicine, Kaunas, Lithuania
3Kaunas University of Technology, Department of Applied Mathematics, Kaunas, Lithuania
4Vilnius University, Neurosurgery, Vilnius, Lithuania
Developed ML‐based algorithms allow to identify CPPopt, (or ABPopt or LLCA/ULCA) values within 24 min (10‐times shorter comparing to 4 h of existing in clinical practice data accumulation time) in the cases when informative physiological ABP/ICP variations are detected. Prospective clinical studies are needed in order to prove the efficiency of developed algorithms.
56‐SEDATION AND CEREBRAL OXIMETRY IN TRAUMATIC BRAIN INJURY: A POTENTIALLY NON‐INVASIVE AVENUE FOR PERSONALIZED APPROACHES IN NEUROCRITICAL CARE?
1University of Manitoba, Biomedical Engineering, Winnipeg, MB, Canada
2University of Manitoba, Surgery, Winnipeg, MB, Canada
3University of Manitoba, Department of Human Anatomy and Cell Science, Winnipeg, MB, Canada
4University of Manitoba, Centre on Aging, Winnipeg, MB, Canada
5Cambridge University, Department of Medicine, Cambridge, United Kingdom
57‐INTRACRANIAL PRESSURE PULSE SHAPE CORRELATES WITH OUTCOME IN TRAUMATIC BRAIN INJURY: A CENTER‐TBI STUDY
1Wroclaw University of Science and Technology, Department of Biomedical Engineering, Wroclaw, Poland
2Wroclaw University of Science and Technology, Department of Computer Engineering, Wroclaw, Poland
3Cambridge University, Clinical Neuroscience, Cambridge, United Kingdom
4Warsaw University of Technology, Institute of Electronic Systems, Warsaw, Poland
5Various intitutions, Various cities, Belgium
58‐CAVUM SEPTI PELLUCIDI IN FORMER AMERICAN FOOTBALL PLAYERS AND ITS ASSOCIATION WITH TRAUMATIC ENCEPHALOPATHY SYNDROME
1Brigham and Women's Hospital, Psychiatry, Boston, MA, United States
2Ludwig‐Maximilians University, Department of Child and Adolescent Psychiatry, Munich, Germany
3Ludwig‐Maximilians University, Graduate School of Systemic Neurosciences, Munich, Germany
4Massachusetts General Hospital, Psychiatry, Boston, MA, United States
5Boston University, Department of Biostatistics, Boston, MA, Germany
6Boston University Alzheimer's Disease Research Center and CTE Center, Neurology, Boston, MA, United States
7Brigham and Women's Hospital, Department of Radiology, Boston, MA, United States
8University of Nevada Las Vegas, Chambers‐Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, Las Vegas, NV, United States
9Arizona State University, Translational Genomics Research Institute, and Arizona Alzheimer's Consortium, Phoenix, AZ, United States
10Boston University, Neurosurgery, Boston, MA, United States
11Boston University, Department of Anatomy & Neurobiology, Boston, MA, United States
59‐PERIVASCULAR SPACE VOLUME IS ASSOCIATED WITH EXPOSURE TO REPETITIVE HEAD IMPACTS AND COGNITIVE IMPAIRMENT IN INDIVIDUALS AT RISK FOR CHRONIC TRAUMATIC ENCEPHALOPATHY
1Brigham and Women's Hospital, Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Boston, MA, United States
2Ludwig‐Maximilians University, cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Munich, Germany
3Boston University, Department of Biostatistics, Boston, MA, United States
4Ludwig‐Maximilians University, Graduate School of Systemic Neurosciences, Munich, Germany
5Boston University, Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston, MA, United States
6Boston University, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston, MA, United States
7Brigham and Women's Hospital, Center for Clinical Spectroscopy, Department of Radiology,, Boston, MA, United States
8Brigham and Women's Hospital, Department of Radiology, Boston, MA, United States
9University of Nevada, Chambers‐Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, Las Vegas, NV, United States
10Arizona State University, Banner Alzheimer's Institute, Translational Genomics Research Institute, and Arizona Alzheimer's Consortium, Translational Genomics Research Institute, and Arizona Alzheimer's Consortium, Phoenix, AZ, United States
11Boston University, Department of Anatomy & Neurobiology, Boston, MA, United States
12Boston University, Neurosurgery, Boston, MA, United States
13Massachusetts General Hospital, Psychiatry, Boston, MA, United States
60‐POST‐TRAUMATIC CRANIAL RECONSTRUCTION USING A 3D PRINTED POLYCAPROLACTONE IMPLANT AFTER BURR HOLE TREPHINATION
1Khoo Tech Puat Hospital, National Healthcare Group, Division of Neurosurgery, Singapore, Singapore
2National University Hospital, National University Health System, Division of Neurosurgery, Singapore, Singapore
Brain injury is a common challenge worldwide. Burr‐hole trephination is used as cranial access for ICP monitoring, EVD drainage, VP shunt insertion, or drainage of chronic subdural haemorrhage. However, the burr hole that remains after surgery posts a safety and cosmetic concern to patients. We would like to share our 10‐year experience of using bioresorbable, 3D printed osteoconductive polycaprolactone implants as burr hole covers. 3D printing enabled the incorporation of a microstructure that mimics cancellous bone.
61‐IMPACT OF SEDATIVE AND VASOPRESSOR AGENTS ON CEREBRAL PHYSIOLOGY AND CEREBROVASCULAR REACTIVITY IN TBI: AN EXPLORATION INTO CONTINUOUS DATA ANALYSIS
1University of Manitoba, Biomedical Engineering, Winnipeg, MB, Canada
2University of Manitoba, Surgery, Winnipeg, MB, Canada
3University of Manitoba, Department of Human Anatomy and Cell Science, Winnipeg, MB, Canada
4University of Manitoba, Centre on Aging, Winnipeg, MB, Canada
5Cambridge University, Department of Medicine, Cambridge, United Kingdom
62‐TIMING OF RETURN TO EXERCISE AFTER RTBI SHAPES INFLAMMATION AND PAIN SENSITIVITY IN ADOLESCENT FEMALE RAT ATHLETES
1University of California, Los Angeles, Neurosurgery, Los Angeles, CA, United States
Repeat mild traumatic brain injury (rTBI) is highly prevalent among adolescent athletes. The post‐injury inflammatory cascade is essential to recovery but can lead to functional deficits. Exercise may ameliorate these deficits, but timing of return to activity is an important consideration. Sex differences introduce additional variables in recovery, and females have been understudied. This study examines how timing of return to exercise after rTBI affects cytokine levels and pain response in adolescent female rats (n = 36; 35 days old). Animals had nightly access to running wheels for 10 days prior to rTBI (2x24hr) or sham injuries. For the 10d post‐injury, rats were assigned to return to running at three timepoints: no running, immediate running, or 3d delay. Neuropathic pain sensitivity was assessed using von Frey filaments at post‐injury day (PID) 1, 3, 5, and 7, and cytokines were measured in cortex, hippocampus, and plasma using a bead‐based multiplex assay. At PID10, injured rats that did not run had elevated pro‐inflammatory cytokine TNF‐alpha in cortex and showed significantly increased pain sensitivity at PID7. Injured rats with 3d delay to exercise showed elevated plasma levels of the anti‐inflammatory cytokine IL‐10. Results suggest that changes in an athlete's activity level after injury may prolong inflammation and impair recovery, while a short delay before activity contributes to an anti‐inflammatory response. Additionally, pro‐inflammatory profiles point to the connection between inflammation and persistence of common pain‐related symptoms in females such as headache.
This work was supported by NIH NS110757, the UCLA BIRC, BrainSPORT, and Easton Labs.
63‐OPTIMIZING CHOICE AND TIMING OF BEHAVIORAL OUTCOME TESTS FOLLOWING REPETITIVE MILD TRAUMATIC BRAIN INJURY: A MACHINE LEARNING‐BASED APPROACH ON MULTIPLE PRECLINICAL EXPERIMENTS
1Karolinska University Hospital, Clinical Neuroscience, Stockholm, Sweden
2Boston Children's Hospital, Division of Emergency Medicine, Boston, MA, United States
3Harvard Medical School, Boston, MA, United States
4Boston University, School of Medicine, Boston, MA, United States
5Karolinska University Hospital, Neurology, Stockholm, Sweden
64‐USING CLEARED TISSUES TO INVESTIGATE THE ROLE OF APOLIPOPROTEIN E4 IN TRAUMATIC VASCULAR INJURY
1University of British Columbia, Pathology and Laboratory Medicine, Vancouver, BC, Canada
2Djavad Mowafaghian Centre for Brain Health, Vancouver, BC, Canada
65‐HEALTH‐RELATED QUALITY OF LIFE AFTER TRAUMA WITH OR WITHOUT TBI – A PROSPECTIVE COHORT STUDY
1Karolinska University Hospital, Clinical Neuroscience, Stockholm, Sweden
2Södersjukhuset, Surgery, Stockholm, Sweden
66‐FUNCTIONAL RECOVERY IN RELATION TO THE POSTTRAUMATIC RESTITUTION OF THE BLOOD‐SPINAL‐CORD‐BARRIER AFTER EXPERIMENTAL SPINAL CORD INJURY IN THE MOUSE
L. Meyer1, L. Waldmann1, N. Taheri1, L. Roolfs1, K. Kersting1, M. Nieminen‐Kelhä1, I. Kremenetskaia1, A. Ghori1, A. Rex2, M. Fehlings3, P. Vajkoczy1,
1Charité, Neurosurgery, Berlin, Germany
2Charité, Experimental Neurology, Berlin, Germany
3Toronto Western Hospital, University Health Network, Neurosurgery, Toronto, ON, Canada
67‐EVOLUTIONARILY CONSERVED BLOOD TRANSCRIPTOMIC SIGNATURES AS DIAGNOSTIC BIOMARKERS AND PHARMACOLOGICAL TARGETS FOR SPINAL CORD INJURY
K. Fond1, M. McCune1, M. Por1, P. Schupp2, A. Torres‐Espin1, A. Lin1, C. Omondi1, A. Ferguson1, J. Bresnahan1, M. Oldham2, M. Beattie1,
1University of California, San Francisco, Brain and Spinal Injury Center, San Francisco, CA, United States
2University of California, San Francisco, Brain Tumor Research Center, San Francisco, CA, United States
68‐RESULTS IN C1‐C2 STABILIZATION ACCORDING TO THE GOEL/HARMS‐TECHNIQUE
1Katholisches Klinikum Koblenz, Spinal Surgery, Koblenz, Germany
The ctaniovertebral junction is mechanical part of the spine that offers the most significant amount of mobility when compared to other segments. The stability and mobility is faciliated by unique morphology of the upper cervical vertebrae. The concept of surgical stabilization was introduced in 1891 by Hadra using wires wrapped around the spinous processes. Since then multiple stabilization techniques with anterior and posterior approaches was invented.
The principle of anterior screw with load support and posterior compression ‐ stabilizationwas introduced. For stabilization and reconstruction after odontoud‐fractures and instabilities we prefer the technique introduces by Goel and Harms with lateral‐mass screw on C1 and pedicle screw on C2. This construct allows an excellent primar stability with recontruction and reduction of the segment. In cases of medullar compression an additional laminectomy of C1 can be performed without loss of stability.
In our Collective we treated between 2/2007‐and 1/2019 56 patients with odontoid‐C1‐C2 istabilities. There were 35 females and 21 males, age 41‐89 years with av. age og 67,8 years. The indication for surgery was: Trauma in 36 cases; PCP in 10; Malformation in 4 and Tumors in 6 cases.
In all cases we achieved a very good primar stability, in one case ‐ a loosening of the screws was observed (after exident). In 4 cases additional construct prolongation up to the occiput was required in the primar setting.
The patient satisfaction was improved by reduction of the neck pain and imprivement of the neurological status (Myelopathia in 8 cases NURICK 3/ 4).
Complicatiions occured in 4 cases with hypalgesia of the neck ‐ due to C2‐leasion. One medial malposition of the C2‐screw leaded to neurological worsening with hemiparalisis‐ the screw was repositioned on the same day with recovery of the neurological symptoms. In one case a neck‐ hematoma and in one case a superficial wound infection occured.
The Goel‐Harms‐ Technique allows a very good anatomical reduction with a high stability of the atlanto‐axial junction. If required ‐ a long construct with fixation up to the occiput can be performed. In our long‐term results‐ a very good stability and high patient tolerance was observed. The special complication rate is low‐ no vascular complications was observed.
69‐EFFICACY AND SAFETY OF ENDOVASCULAR VERTEBRAL ARTERY OCCLUSION FOR TRAUMATIC VERTEBRAL ARTERY INJURY
1University of Tsukuba Hospital, Neurosurgery, Tsukuba, Japan
2University of Tsukuba, Division of Stroke Prevention and Treatment, Faculty of Medicine, Tsukuba, Japan
3University of Tsukuba, Department of Orthopedic Surgery, Tsukuba, Japan
4University of Tsukuba, Neurosurgery, Tsukuba, Japan
5University of Tsukuba, Emergency and Critical Care, Tsukuba, Japan
70‐IMPACT OF HYPERTONIC SOLUTIONS TREATMENT IN SYMPTOMATIC MILD TRAUMATIC BRAIN INJURY PATIENTS WITH NON‐SURGICAL ABNORMAL CT FINDINGS
1UKJ, Jena, Germany
2MediTech, Cali, Colombia
3San Martin University, Cali, Colombia
4Cambridge University, Cambridge, Germany
71‐USING COMPLEXITY ANALYSIS OF RESTING STATE FUNCTIONAL MAGNETIC RESONANCE IMAGING (RS‐FMRI), AND MACHINE LEARNING TO DETECT FUNCTIONAL DAMAGE IN PATIENTS WITH CONCUSSION
1TBIFinder inc., Hamilton, Canada
2McMaster University, Department of Electrical and Computer Engineering, Hamilton, Canada
3St. Joseph's Healthcare Hamilton, Imaging Research Centre, Hamilton, Canada
4University of Toronto, Department of Physical Medicine & Rehabilitation, Toronto, Canada
5Toronto Rehabilitation Institute, Toronto, Canada
6neurorad.ch, Zurich, Switzerland
7University hospital of Schleswig‐Holstein, Kiel, Germany
8McMaster University, School of Biomedical Engineering, Hamilton, Canada
9McMaster University, Department of Radiology, Hamilton, Canada
72‐FUNCTIONAL OUTCOMES AND WELLBEING AFTER TRAUMATIC BRAIN INJURY IN ELDERLY PATIENTS: A 6‐MONTH FOLLOW‐UP PROSPECTIVE STUDY
1University Hospital KU Leuven, Biomechanics Section, Leuven, Belgium
2University Hospital KU Leuven, Neurosurgery, Leuven, Belgium
73‐SEX STEROIDS THERAPY USING NANOMEDICINE: A PATH FOR NEUROTRAUMA?
1Clinique Romande de Réadaptation, Physical Medicine and Rehabilitation, Sion, Switzerland
74‐THREE‐DIMENSIONAL PRINTING IN CRANIAL TRAUMA: HISTORY AND FUTURE APPLICATIONS IN CRANIOPLASTY SURGERY
1Cambridge University, Department of Suregry, Cambridge, United Kingdom
2University Leicester Hospital, Leicester, United Kingdom
Three‐dimensional (3D) printing has gained huge traction in medicine following advances in both biomaterials as well as surgical techniques. First developed in the early 1980s, then described as "stereolithography", 3D printing techniques encompass the deposition of biomaterials in successive layers, known as additive manufacturing. Over the last four decades, advances in radiological imaging and biomaterial properties have bolstered the potential of implantable prostheses, of which may aid neurosurgeons in patients with non‐constructible skull defects.
3D printing is a novel technology that has the opportunity to revolutionise the fields of surgery and medicine; applied to neurotrauma, new and upcoming biomaterials may provide scaffolding and protection of the brain in patients that have had previously non‐reconstructible deficits to the cranial vault.
75‐NOVEL, INTERESTING, SURPRISING AND USEFUL PROPERTIES OF A PANEL OF NF‐L MONOCLONAL ANTIBODIES
1University of Florida, Neuroscience, Gainesville, FL, United States
2EnCor Biotechnology Inc., Gainesville, FL, United States
3University of Florida, McKnight Brain Institute, Gainesville, FL, United States
4University of Florida, Physical Therapy, Gainesville, FL, United States
5Breathing Research and Therapeutics Center, Gainesville, FL, United States
Neurofilament light protein (NF‐L) can be detected at informative levels in blood, CSF and other fluids in studies of a variety of neurodegenerative states using excellent commercial assays from Uman Diagnostics, Quanterix and others. We have fully characterized the two key monoclonal antibody reagents used in these assays. Surprisingly, neither antibody recognizes typical neurofilament rich profiles in healthy neurons and their processes in sectioned material or in neural cultures, instead recognizing a minority of processes which have the appearance of neurodegeneration. In stark contrast, following a mid‐cervical spinal cord contusion injury in rats, both antibodies reveal numerous strongly stained nerve fibers in regions expected to contain compromised processes. Many of these processes appear beaded, sinusoidal or discontinuous as expected for degenerating axons. We localized the epitopes for both Uman antibodies to a short NF‐L peptide and made novel monoclonal and polyclonal antibodies to this region which share these interesting selective staining properties. The unmasking of the degeneration specific epitopes appears to be due to proteolysis and can be mimicked by treating sections of healthy tissue with proteases, which results in previously unreactive NF‐L containing profiles becoming strongly reactive with this specific type of NF‐L antibody. We have also developed specific antibodies which recognizes a proteolytically labile site on NF‐L in healthy axons which disappears in degenerating processes, allowing positive identification of both healthy and degenerated processes. These reagents are robust, excellent, novel and specific markers of neurodegeneration of wide utility in future studies of CNS disease and injury.
76‐COMPARISON OF NEUROVASCULAR PATHOPHYSIOLOGY FOLLOWING LOW LEVEL PRIMARY BLAST AND FLUID PERCUSSION INJURY
1St. Michael's Hospital, Trauma Research, Toronto, ON, Canada
2University of Toronto, Anesthesia, Toronto, ON, Canada
77‐CHARACTERIZATION OF HMGB1 MEDIATED NEUROINFLAMMATION AFTER MODELED TBI
1University of Toronto, Institute of Medical Science, Toronto, ON, Canada
2St. Michael's Hospital, Critical Care, Toronto, ON, Canada
3Li Ka Shing Knowledge Institute, Trauma Research, Toronto, ON, Canada
Traumatic brain injury (TBI) is a leading cause of death and disability world‐wide. Secondary injury due to aberrant immune response can contribute to poor outcome. Neuroinflammation is a major contributor to secondary injury mechanisms and is a potential target for therapeutic intervention. We propose that HMGB1 and its receptor RAGE contribute negatively to the neuroinflammatory response after TBI. HMGB1, a chromatin‐associated protein located in the nucleus, acts as a cytokine, and binds to the RAGE receptor resulting in activation of NF‐kB mediated pro‐inflammatory pathways. We have characterized the expression of HMGB1 and RAGE expression in control and injured rats. We used immunohistochemistry and western blot analysis to examine expression at 24 hours, 7 days, and 2 weeks post‐injury. We observed expression and translocation of RAGE following injury in neurons and microglia. To further elucidate the signalling pathways associated with HMGB1 and RAGE expression after injury we are using microglia and primary neuronal cell cultures to examine changes in expression following in vitro stretch trauma. We propose to use inhibitors of RAGE and HMGB1 to parse out the signalling mechanisms involved in expression changes after injury. Furthermore, we aim to determine whether conditioned media from injured neurons and microglia is sufficient to induce a feedforward mechanism of HMGB1 release in non‐injured cells. Our preliminary data suggest a role for HMGB1 and its receptor, RAGE, in the inflammatory response following TBI. These molecules may be potential targets for therapeutic intervention.