Restorative Neurology and Neuroscience

Purpose: We investigated the motor recovery mechanism of a stroke patient using functional MRI (fMRI) and diffusion tensor image tractography (DTT).

Methods: A 60 year-old woman with right corona radiata infarct presented with complete paralysis of the left upper extremity. The motor function of the affected upper extremity recovered slowly for 6 months to a point of nearly normal function. The motor function of the patient was evaluated by fMRI and DTT at 6 months from the onset. FMRI was performed at 1.5 T with timed hand grasp-release movements. DTT was performed using 1.5 T with a synergy-L Sensitivity Encoding head coil. Three dimensional reconstructions of the fiber tracts were obtained with FA < 0.3, angle > 45° as termination criteria.

Results: The contralateral primary sensorimotor cortex (SM1) was activated during both affected (left) and unaffected hand movements. DTT showed that the tracts originated from either SM1; the tracts then descended along the known pathway of the corticospinal tract, with the exception that the tract of the affected (right) hemisphere descended along the posterior portion of the infarcted corona radiata.

Conclusions: It seems that the motor function of the affected upper extremity was reorganized to the posterior portion of the infarcted corona radiata. This finding may reflect functional reorganization of the motor pathway following corticospinal tract damage. This appears to be one motor recovery mechanism of subcortical infarct.

Purpose: This review summarizes possible spinal reflexes involved in micturition control as well as current treatments for lower urinary tract dysfunction after spinal cord injury (SCI) in an effort to further promote the development of new treatments for people with SCI.

Methods: A systematic literature search was conducted on the Medline database, and on the Web of Science.

Results: After SCI normal functions of the lower urinary tract are lost. The detrusor contracts frequently even at a small bladder volume, which results in urinary incontinence. In addition, the hyperactive bladder can not empty well because the urethral sphincter contracts simultaneously with the bladder (detrusor sphincter dyssynergia), which results in a large residual volume of urine. The malfunction of the lower urinary tract after SCI is caused by remaining and newly emerged bladder and urethral sphincter spinal reflexes. Current treatments have either limited success or troublesome side effects, and many new treatments are under development.

Conclusions: In order to restore the functions of the lower urinary tract after SCI, efforts should be directed at re-establishing the coordination between the spinal reflex control of bladder and urethral sphincter using either pharmacological or neurophysiological approaches.

Purpose: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or "statins", are used as cholesterol-lowering agents worldwide. This review, focused on recent experimental and clinical data, summarizes general mechanisms of statin actions underlying neuroprotective effects in the central nervous system (CNS) and presents evidence for putative mechanisms involving heat shock proteins and the survival-related PI-3K/Akt pathway that may be beneficial for the treatment of neurological disorders.

Methods: We carried out a medline search on statin actions, with respect to biochemical pathways and signal transduction on the one hand, and clinical studies in neurologic and retinal diseases on the other hand. Novel experimental data obtained in a rat model of axonal CNS injury were also included.

Results: Statins exert multiple effects on endothelial function, cell proliferation, inflammatory response, immunological reactions, platelet function, and lipid oxidation. These "pleiotropic actions" are independent of cholesterol lowering and appear to be beneficial in the context of brain injury. Several mechanisms of statin actions underlying neuroprotective effects may also involve heat shock proteins and the survival-related PI-3K/Akt pathway.

Conclusions: Available data suggest that statins may be of potential therapeutic use in a variety of diseases of the CNS including ischemic stroke, Alzheimer's disease, multiple sclerosis and some forms of retinal and eye diseases. Before general recommendations can be made and specific therapeutic approaches can be developed, more reliable clinical data and studies are required, and possible side effects must be carefully evaluated.

Purpose: After a spinal cord injury (SCI), which was complete, deafferentation of the body representation caudal to the lesion height results in drastic changes in the cortical representation. The underlaying processes are poorly understood.

Methods: We investigated cortical representation sites of upper limb muscles using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in five patients suffering from thoracic complete SCI and one with an incomplete SCI in the height of L1.

Results: In comparison to healthy controls fMRI demonstrated a displacement of elbow movement representations in the precentral gyrus in patients with complete SCI into the direction of the deafferented cortical thoracic representation. Changes increased with time after the incidence of SCI. TMS revealed reduced excitability and prolonged silent periods for muscles more distant to the deafferented area.

Conclusions: Whereas fMRI demonstrated changes in representation sites adjacent to the deafferented area, TMS excitability changes were also observed more distant to the deafferented area and silent periods were prolonged in comparison to healthy controls. TMS changes might depend on both: the distance to the deafferented area and the time of persistence of deafferentation.

Purpose: As deficits in memory and cognition are commonly observed in survivors of traumatic brain injury (TBI), causing reduced quality of life for the patient, a major goal in experimental TBI research is to identify and evaluate cognitive dysfunction. The present study assessed the applicability of the serial Morris water maze (MWM) test to determine cognitive function following experimental TBI in the same group of rats which is particularly important for long-term studies and increasingly valuable for the evaluation of novel treatment strategies.

Methods: Male Sprague-Dawley rats (n=27) were anesthetized and subjected to either sham injury (n=9) or lateral fluid percussion (FP) brain injury of moderate severity (n=18). At 4 weeks post-injury, animals were trained in a water maze over 3 days (acquisition/learning phase) to find a submerged platform. At 8 weeks post-injury the hidden platform was then moved to the opposite quadrant, and animals were trained to find the new position of the platform over 3 days. Forty-eight hours later, animals were tested for memory retention in a probe trial in which the platform was not present.

Results: Brain-injured animals had significant learning impairment (p<0.0001), shifted-learning impairment (p<0.001) and memory retention deficits (p<0.01) in comparison to their sham-injured counterparts over the 8 week testing period. Swim speed and distance were not significantly altered by brain injury at any time point.

Conclusion: The validation of this testing paradigm using a clinically relevant experimental brain injury model is an important addition to behavioral outcome testing.

Purpose: We have previously shown that the stimulation of limbic structures related to affective life such as the amygdale can improve and reinforce neural plastic processes related to hippocampus-dependent forms of explicit memory, as spatial memory and LTP. We now assessed whether this effect is restricted to the mentioned structure and memory type, or represents a more general form of modulatory influence.

Methods: Young, male Sprague Dawley rats were implanted stereotactically with one electrode in the basolateral amygdala (BLA) and trained to acquire a motor skill using their right anterior limb. A group of animals received 3 trains of 15 impulses at the BLA 15 minutes after each daily training session. A second group of implanted animals was handled in the same way, but not stimulated, while a third group was not implanted. After reaching the training criterion the left motor cortex was mapped by the observation of the movements induced by stimuli applied in discrete points of the cortex.

Results: Cortical representation of the anterior limb was increased in all trained animals, showing that the motor cortex is involved in the acquisition of the new skill. Animals receiving stimulation of the BLA showed similar cortical changes, but learned faster than non-stimulated controls.

Conclusions: Reinforcement of neural plasticity by the activation of the amygdala is not restricted to hippocampus-dependent explicit memory, but it might represent a universal mechanism to modulate plasticity.

Purpose: To study rehabilitation outcome in a chronic visual field defect patient using positron emission tomography (PET) imaging, clinical, and neurophysiological measures.

Methods: A patient with chronic visual field defect was rehabilitated using a computer program over a three-month period. Evaluations of rehabilitation effects were done before and after training, and after a three-month follow-up with perimetry, visual evoked potentials (VEP), subjective questionnaire, and PET activation studies of regional cerebral blood flow (rCBF).

Results: In perimetry, the visual field increased during the training, and the patient also experienced subjective improvement. In VEP, a previously absent P100 component was identified after the training. In PET, increases in rCBF were diffuse immediately after the training, and more occipital after the late follow-up. A significant positive correlation between the increase in rCBF and improvement in clinical measures was found in the lingual gyrus in the contralesional hemisphere.

Conclusions: All clinical measures showed improvement after rehabilitation, and this was maintained during the follow-up. In PET, a more generalized effect, found at the beginning, later concentrated in the occipital cortex. The results suggest that visual training may cause plastic changes in the brain, and that these changes can be detected both with clinical measures and with functional imaging.