Restorative Neurology and Neuroscience

Background: Intensive, task-oriented motor training has been associated with neuroplastic reorganization and improved upper extremity movement function after stroke. However, to optimize such training for people with moderate-to-severe movement impairment, pharmacological modulation of neuroplasticity may be needed as an adjuvant intervention.

Objective: Evaluate safety, as well as improvement in movement function, associated with motor training paired with a drug to upregulate neuroplasticity after stroke.

Methods: In this double-blind, randomized, placebo-controlled study, 12 subjects with chronic stroke received either atomoxetine or placebo paired with motor training. Safety was assessed using vital signs. Upper extremity movement function was assessed using Fugl-Meyer Assessment, Wolf Motor Function Test, and Action Research Arm Test at baseline, post-intervention, and 1-month follow-up.

Results: No significant between-groups differences were found in mean heart rate (95% CI, –12.4–22.6; p = 0.23), mean systolic blood pressure (95% CI, –1.7–29.6; p = 0.21), or mean diastolic blood pressure (95% CI, –10.4–13.3; p = 0.08). A statistically significant between-groups difference on Fugl-Meyer at post-intervention favored the atomoxetine group (95% CI, 1.6–12.7; p = 0.016).

Conclusion: Atomoxetine combined with motor training appears safe and may optimize motor training outcomes after stroke.

Purpose: As well as obtaining confirmation of the magnocellular system involvement in developmental dyslexia (DD); the aim was primarily to search for a possible involvement of the parvocellular system; and, furthermore, to complete the assessment of the visual chromatic axis by also analysing the koniocellular system.

Methods: Visual evoked potentials (VEPs) in response to achromatic stimuli with low luminance contrast and low spatial frequency, and isoluminant red/green and blue/yellow stimuli with high spatial frequency were recorded in 10 dyslexic children and 10 age- and sex-matched, healthy subjects.

Results: Dyslexic children showed delayed VEPs to both achromatic stimuli (magnocellular-dorsal stream) and isoluminant red/green and blue/yellow stimuli (parvocellular-ventral and koniocellular streams). To our knowledge, this is the first time that a dysfunction of colour vision has been brought to light in an objective way (i.e., by means of electrophysiological methods) in children with DD.

Conclusion: These results give rise to speculation concerning the need for a putative approach for promoting both learning how to read and/or improving existing reading skills of children with or at risk of DD. The working hypothesis would be to combine two integrated interventions in a single programme aimed at fostering the function of both the magnocellular and the parvocellular streams.

Background: Acquired brain injuries (ABI) have devastating effects for the affected individual as well as society. Many studies have investigated the effect of different monotherapies. However, functional recovery is typically only partial. One possible strategy to promote a greater degree of recovery is to apply monotherapies in combination with one or more treatments.

Objective: The objective of this systematic review is to investigate if approaches combining enriched environment (EE), exercise, or task-specific training with other monotherapies, further enhance the degree of recovery after ABI.

Method: Scopus, PsychINFO, and PubMed databases were searched in March 2016 with the following search strings: exercise (or) enriched environment (or) environmental enrichment (or) rehabilitation (and) traumatic brain injury (or) ischemia (or) stroke (and) rat (or) rodent. Studies were included if they (1) were in English, (2) used adult animals subjected to brain injury, (3) included EE, and/or exercise, and/or task-specific training as post-injury treatment strategies, (4) included at least one group receiving another monotherapy. Out of 2.168 hits, 29 studies fulfilled the inclusion criteria.

Results: Despite several trends for enhanced recovery after combined therapies, this systematic review of 29 studies does not indicate that combined therapies confer consistent combined effects on motor, cognitive, or cerebral recovery according to present criteria for combined effect.

Conclusion: Combined treatments continue to provide hope for enhanced recovery after ABI, however, the research area is in its infancy. This systematic review does not provide conclusive evidence. This is likely due to sparse knowledge regarding optimal treatment parameters. Combined treatments, however, hold the best promise regarding treatment of the complex changes induced by ABI.

Background: A clear relationship exists between oxidative stress and disruption of blood-brain barrier (BBB) during cerebral ischemia, in which aging may exacerbate the extent of leakage. Here, we aim to examine the potential role of a water-soluble carotenoid-based antioxidant crocin on BBB damage in aged rats following cerebral ischemia.

Methods: A two months oral administration of crocin was applied to 24-month-old rats followed by an induction of brain ischemia by middle cerebral artery occlusion (MCAO). Brain infarction volume, water content, and neurological behavior assessments were measured in these animals at 24 hours after MCAO as compared to vehicle-treated controls. Evans blue dye extravasation assay was used to evaluate the BBB integrity. The levels of tight junction proteins, oxidative stress, and MMP (matrix metalloproteinases) activities were also determined in the ipsilateral brains of the MCAO-treated rats.

Results: MCAO-induced brain injury was alleviated by the pretreatment of crocin. Crocin-treated animals also showed the preserved BBB function in the presence of ischemic injury. The loss of tight junction proteins and enhanced NADPH oxidase in the ipsilateral brains of the MCAO-treated rats were both reduced by crocin. Finally, the induction of MMP-2 and MMP-9 by cerebral ischemia was partially blocked by crocin in aged rats.

Conclusion: These findings indicate that crocin or related antioxidants may protect against cerebral ischemia of elderly patients by maintaining the integrity of BBB in aged rats, an effect likely through repressing the activation of matrix metalloproteinase pathway.

Background: Patients suffering from chronic disorders of consciousness (DOC), including minimally conscious state (MCS) and unresponsive wakefulness syndrome (UWS), typically show an awareness impairment paralleled by a significant reflex hyper-excitability, which depend on the cortical deafferentation following brain-damage-induced thalamocortical system deterioration. Nonetheless, recent studies have shown a residual preservation of cortico-subcortical pathways that may sustain residual fragments of awareness in some DOC patients.

Objective: The aim of our study was to assess whether the cortical modulation of auditory stapedial reflex (ASR) could be a marker of a higher degree of brain network connectivity, which is a fundamental prerequisite for awareness generation and maintenance.

Methods: We applied a repetitive transcranial magnetic stimulation (rTMS) protocol over the primary auditory area and measured the neuromodulation effects on ASR threshold (ASRt) in a DOC sample and a healthy control group (HC).

Results: We observed an ASRt reduction in all the HC and MCS individuals, in parallel to a better sound-induced motor responsiveness in MCS sample, while all the UWS patients, but two, did not show any significant ASRt modulation.

Conclusion: We hypothesize that our conditioning protocol may have entrained and potentiated some spared cortico-subcortical networks that sustained the clinical and electrophysiological amelioration we found. Our data electrophysiologically demonstrate for the first time that primary the auditory area can influence ASR elicitation, and such finding may support the DOC differential diagnosis.

The already established and widely used intravenous application of recombinant tissue plasminogen activator as a re-opening strategy for acute vessel occlusion in ischemic stroke was recently added by mechanical thrombectomy, representing a fundamental progress in evidence-based medicine to improve the patient’s outcome. This has been paralleled by a swift increase in our understanding of pathomechanisms underlying many neurovascular diseases and most prevalent forms of dementia. Taken together, these current advances offer the potential to overcome almost two decades of marginally successful translational research on stroke and dementia, thereby spurring the entire field of translational neuroscience. Moreover, they may also pave the way for the renaissance of classical neuroprotective paradigms.

This review reports and summarizes some of the most interesting and promising recent achievements in neurovascular and dementia research. It highlights sessions from the 9th International Symposium on Neuroprotection and Neurorepair that have been discussed from April 19th to 22nd in Leipzig, Germany. To acknowledge the emerging culture of interdisciplinary collaboration and research, special emphasis is given on translational stories ranging from fundamental research on neurode- and -regeneration to late stage translational or early stage clinical investigations.

Background: Noninvasive brain stimulation (NBS) using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) has recently been adopted for modulating motor function in stroke patients.

Objective: We investigated the effect of simultaneous dual-mode stimulation using rTMS and tDCS over the bilateral primary motor cortices (M1) to assess its efficacy as compared to single stimulation using rTMS for the recovery of motor function in subacute stroke patients.

Methods: Thirty subacute stroke patients were recruited in this study. In the dual-mode stimulation group, 10 Hz rTMS (90% of resting motor threshold, 1,000 pulses) was applied over the ipsilesional M1 for 20 minutes with the simultaneous application of cathodal tDCS (2 mA) on the contralesional M1. The single stimulation group underwent 10 Hz rTMS without tDCS. Ten daily sessions were conducted for two consecutive weeks. The total Fugl-Meyer (FMA-T), upper limb (FMA-UL), and lower limb (FMA-LL) scores were measured before, after, and two months later.

Results: The FMA-T and FMA- UL were significantly improved over time in both the dual and single stimulation group (p < 0.05). However, there were significant group and time interaction effects in both the FMA-T and FMA-UL (p < 0.05). Post-hoc analysis showed that the mean changes in the FMA-T and FMA-UL were significantly better in the dual-mode stimulation group.

Conclusion: Dual-mode NBS with the simultaneous application of 10 Hz rTMS and cathodal tDCS over the bilateral M1s was safe and superior to 10 Hz rTMS alone for improving motor function in subacute stroke patients.

Background and Purpose: Deficits of self-awareness (SA) are very common after severe acquired brain injury (sABI), especially in traumatic brain injury (TBI), playing an important role in the efficacy of the rehabilitation process. This pilot study provides information regarding two structured group therapies for disorders of SA.

Methods: Nine patients with severe TBI were consecutively recruited and randomly assigned to one SA group therapy programme, according either to the model proposed by Ben-Yishay & Lakin (1989) (B&L Group), or by Sohlberg & Mateer (1989) (S&M Group). Neuropsychological tests and self-awareness questionnaires were administered before and after a 10 weeks group therapy.

Results: Results showed that both SA and neuropsychological functioning significantly improved in both groups.

Conclusion: It is important to investigate and treat self-awareness, also to improve the outcome of neuropsychological disorders. The two group therapies proposed seem to be specific for impulsivity and emotional dyscontrol and for cognitive disorders.

Background: Appropriate management of pain after an injury or surgical procedure has been shown to improve patient outcomes. While infrequent, nerve damage resulting from regional anesthesia can be devastating, however the mechanism remains unknown. Local anesthetics are neurotoxic yet are frequently applied to sites where peripheral nerves are regenerating. Therefore, understanding their effects on injured and growing neurons may have important implications for clinical practice.

Objective: The purpose of this study was to determine if local anesthetics exacerbate the rate of motoneuron death following axotomy.

Methods: Mice were subjected to a unilateral transection of the facial motor nerve, and either normal saline, 2% lidocaine, or 0.75% bupivacaine was placed at the injury site. Four weeks post-axotomy, percent survival was determined by comparing the number of motoneuron cell bodies on the injured side and the uninjured control side.

Results: The average facial motoneuron survival in the saline, lidocaine, and bupivacaine groups 4 weeks after axotomy was 80%, 78% and 35%, respectively.

Conclusion: Our data suggest that bupivacaine exacerbates levels of cell death in injured motoneurons. It has been proposed that once a nerve is damaged, it becomes more susceptible to injury elsewhere along the nerve. Thus, an improved understanding of the effects of local anesthetics on neuron survival and axon regeneration may lead to strategies to identify patients at higher risk for permanent neural deficits after peripheral nerve blocks and/or decrease the risk of neural deficit following peripheral nerve blocks.