Restorative Neurology and Neuroscience - Volume 23, issue 5-6

Authors: Jang, Sung Ho | Kwon, Yong-Hyun | You, Sung H | Song, Jun Chan | Lee, Mi Young | Kim, Joong Hwi | Park, Kyung Hee | Cho, Yoon Woo

Article Type: Research Article

Abstract: Purpose: Peri-lesional reorganization is a motor recovery mechanism after brain injury. The object of this study was to demonstrate the peri-lesional reorganization, using functional MRI (fMRI) and diffusion tensor tractography (DTT). Methods: Six control subjects and a 53 year-old woman with left primary sensori-motor cortex (SM1) and underlying deep white matter injury were evaluated. The patient presented with complete paralysis of the right hand after the resection of a meningioma on the left SM1. …The motor function of the affected hand had recovered slowly the extent of her being able to overcome some resistance for 6 months. At 2 years after the operation, fMRI was performed at 1.5 T in parallel with timed finger flexion-extension movements in all subjects and DTT was performed only in the patient. Results: The contralateral SM1 centered on the precentral knob was activated during hand movements of unaffected (left) side or control subjects. However, the medial area of the injured SM1 was activated during affected (right) hand movements. DTT of the affected (left) hemisphere originated from the medial area of the injured SM1 and descended along the medial side of injured deep white matter. Conclusions: It seems that the motor function of the affected hand was reorganized into the medial area of the injured SM1 and deep white matter in this patient. Show more

Keywords: Functional MRI, diffusion tensor MRI, motor recovery, brain injury, cortical reorganization

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 5-6, pp. 265-269, 2005

Authors: Platz, T. | Kim, I.-H. | Engel, U. | Pinkowski, C. | Eickhof, C. | Kutzner, M.

Article Type: Research Article

Abstract: Purpose. To assess the effects of d-amphetamine on motor facilitation and recovery in stroke patients with mild arm paresis receiving the Arm Ability training. Methods. Thirty-one stroke patients with mild arm paresis were randomly assigned to either (a.) receiving placebo or (b.) d-amphetamine twice a week 2 hours before Arm Ability training sessions for three weeks. Main outcome measure: time needed to perform TEMPA tasks, a measure of upper extremity performance reflecting everyday life …tasks. Secondary measures: aimed movements, tapping, and a 10 m walkway as well as motor performance during training sessions. Results. The interim efficacy analysis of 26 stroke patients who completed the study intervention showed overall arm motor recovery both from pre to post test after 3 weeks of training and from pre test to follow-up 1 year later. No superior effect of d-amphetamine over placebo could be substantiated for either motor facilitation during training or motor recovery (post training or long-term). D-amphetamine exerted mild effects on blood pressure. Serious adverse events were not observed. Conclusions. d-Amphetamine failed to facilitate motor performance during training sessions, to promote skill acquisition with training tasks, and most importantly to enhance motor recovery among patients with mild arm paresis after stroke. Show more

Keywords: Arm, stroke, rehabilitation, training, recovery, amphetamine, clinical trial

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 5-6, pp. 271-280, 2005

Authors: Fink, Martina | Churan, Jan | Wittmann, Marc

Article Type: Research Article

Abstract: Purpose: The relationship between auditory temporal-order perception and phoneme discrimination has been discussed for several years, based on findings, showing that patients with cerebral damage in the left hemisphere and aphasia, as well as children with specific language impairments, show deficits in temporal-processing and phoneme discrimination. Over the last years several temporal-order measurement procedures and training batteries have been developed. However, there exists no standard diagnostic tool for adults that could be …applied to patients with aphasia. Therefore, our study aimed at identifying a feasible, reliable and efficient measurement procedure to test for auditory-temporal processing in healthy young and elderly adults, which in a further step can be applied to patients with aphasia. Methods: The tasks varied according to adaptive procedures (staircase vs. maximum-likelihood), stimuli (tones vs. clicks) and stimulation modes (binaural- vs. alternating monaural) respectively. A phoneme-discrimination task was also employed to assess the relationship between temporal and language processing. Results: The results show that auditory temporal-order thresholds are stimulus dependent, age related, and influenced by gender. Furthermore, the cited relationship between temporal-order threshold and phoneme discrimination can only be confirmed for measurements with pairs of tones. Conclusion: Our results indicate, that different norms have to be established for different gender and age groups. Furthermore, temporal-order measurements with tones seem to be more suitable for clinical intervention studies than measurements with clicks, as they show higher re-test reliabilities, and only for measurements with tones an association with phoneme-discrimination abilities was found. Show more

Keywords: Auditory-temporal processing, phoneme discrimination, aphasia, age difference, sex difference, diagnostics

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 5-6, pp. 281-296, 2005

Authors: Allred, R.P. | Maldonado, M.A. | Hsu and, J.E. | Jones, T.A.

Article Type: Research Article

Abstract: Purpose: Unilateral lesions of the sensorimotor cortex (SMC) in adult rats cause major behavioral changes in the ipsilesional, "less-affected" forelimb. An increase in function and reliance on this forelimb can aid compensation for contralesional impairments, but may also promote disuse and reduced functionality of the impaired forelimb. We hypothesized that training focused on the ipsilesional forelimb following a unilateral SMC lesion would reduce the efficacy of later motor rehabilitative training of the impaired …forelimb. Methods: Rats with ischemic SMC lesions were trained on a skilled reaching task with the ipsilesional forelimb (PriorT) or received control procedures (Cont) for 10 days. Both groups were then trained with the impaired forelimb on the same reaching task for 10 days. Results: In comparison with Cont, PriorT rats had little improvement on the reaching task with the impaired forelimb and had a more enduring disuse of the impaired forelimb for postural support behaviors. Lesion sizes were similar between groups. Conclusions: Behavioral experience with the less-affected forelimb early after unilateral SMC lesions has the potential to increase disuse and dysfunction of the impaired forelimb, consistent with a training-induced exacerbation of learned non-use. These findings are suggestive of competitive processes in experience-dependent neural restructuring after brain damage. Show more

Keywords: Ischemia, caudal forelimb representation area, motor cortex, motor rehabilitation, skilled reaching, learned non-use

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 5-6, pp. 297-302, 2005

Authors: Heiduschka, Peter | Fischer, Dietmar | Thanos, Solon

Article Type: Research Article

Abstract: Purpose: Following optic nerve damage, retinal ganglion cells (RGCs) fail to regenerate their axons and soon undergo apoptosis. However, many RGCs survive axotomy and regenerate lengthy axons after a lens injury (LI). If the cut optic nerve is re-sutured, RGC axons grow into the distal part of the optic nerve and reach their natural targets within the thalamus and midbrain. In this study, we check time-dependence and extent of restoration of flash visual evoked potentials (FVEPs) …to examine the functional relevance of the regenerated retinogeniculate pathway. Methods: The optic nerve in adult rats was cut and re-sutured. The lens was injured transsclerally using a pointed glass capillary. FVEPs were measured starting at the time point of surgery, and then repeatedly up to an age of several months. Results: Detectable FVEPs appeared approximately ten weeks after the surgery, and their amplitudes increased during the next months to reach eventually 15–40% of their values before surgery. Conclusions: Partial restoration of FVEPs indicates that some regenerating RGC axons have "bridged" the distance between the eye and the central targets forming a functional re-connection of the corresponding RGC with thalamic target neurones to elicit recordable activation of the visual cortex Show more

Keywords: Rat retina, axotomy, optic nerve regeneration, lens injury, visual evoked potentials, functional recovery

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 5-6, pp. 303-312, 2005

Authors: Blits, Bas | Kitay, Brandon M. | Farahvar, Arash | Caperton, Caroline V. | Dietrich, W. Dalton | Bartlett Bunge, Mary

Article Type: Research Article

Abstract: Purpose: Stem cells represent an attractive source for cell replacement therapy in neurological disorders due to their self-renewal and multi-potency. Genetic manipulation of these cells may allow controlled release of therapeutic proteins, suppress immune rejection, or produce essential neurotransmitters. Furthermore, when the expression cassette is incorporated into the host genome ex vivo, this technique also may be used as a method to trace cells following implantation into tissues of interest. Methods: …We explored the possibility of transducing pluripotent fetal rat cortical neural progenitor cells (NPCs) using lentiviral vectors encoding the green fluorescent protein (GFP) or neurotrophic factors (BDNF, CNTF, D15A, GDNF, MNT and NT-3) prior to implanting these cells into the contused spinal cord or injured brain. Results: In vitro staining of these cells for neural markers (such as nestin, GFAP, Tuj-1 and RIP) after transduction did not reveal any significant difference from non-transduced cells. When they were transduced with a vector encoding CNTF or MNT, however, cells started expressing GFAP in vitro. Following delayed (1 week) implantation into the lesion site of the moderately contused rat spinal cord or the injured brain, transduced cells survived up to 12 weeks post-implantation (the longest time point examined) and most of the NPCs turned into an astrocytic phenotype in the spinal cord, but not in the brain. Nestin and GFP positive cells were detected in the brain, but not in the spinal cord lesion. GFP positive cells in the spinal cord migrated rostrally and caudally from the lesion/implantation site towards uninjured tissue. Conclusions: Novel findings in this study are the longterm expression of a foreign gene in NPCs using lentiviral vectors; this enabled tracking of the cells following implantation. This expression also allowed the observation that NPCs developed differently in the injured spinal cord and brain. Moreover, NPCs could be transduced to overexpress neurotrophic factors. In sum, NPC survival and the long-term transgene expression that allows easy tracking of migrating cells make NPCs promising candidates for implantation into the injured spinal cord or brain and a potentially powerful tool to enhance regeneration when transduced ex vivo to produce therapeutic molecules. Show more

Keywords: Neural precursor cell, lentiviral vector, injury, CNS, green fluorescent protein, transplantation

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 5-6, pp. 313-324, 2005

Authors: Jang, Sung Ho | You, Sung H. | Kwon, Yong-Hyun | Hallett, Mark | Lee, Mi Young | Ahn, Mi Young

Article Type: Research Article

Abstract: Purpose: Recovery mechanisms supporting upper extremity motor recovery following stroke are well established, but cortical mechanism associated with lower extremity motor recovery is unknown. The aim of this study was to assess cortical reorganization associated with lower extremity motor recovery in a hemiparetic patient. Methods: Six control subjects and a 17 year-old woman with left intracerebral hemorrhage due to an arterio-venous malformation rupture were evaluated. The motor function of the paretic (left) hip and …knee had recovered slowly to the extent of her being able to overcome gravity for 10 months after the onset of stroke. However, her paretic upper extremity showed no significant motor recovery. Blood oxygenation level dependent (BOLD) functional MRI at 1.5 Tesla was used to determine the acutual location of cortical activation in the predefined regions of interest. Concurrently, Diffusion Tensor Imaging (DTI) in combination with a novel 3D-fiber reconstruction algorithm was utilized to investigate the pattern of the corticospinal pathway connectivity between the areas of the motor stream. All subjects' body parts were secured in the scanner and performed a sequential knee flexion-extension with a predetermined angle of 0–60° at 0.5 Hz. Results: Controls showed anticipated activation in the contralateral sensorimotor cortex (SM1) and the descending corticospinal fibers stemming from motor cortex. In contrast to control normal subjects, the stroke patient showed fMRI activation only in the unaffected (right) primary SM1 during either paretic or nonparetic knee movements. DTT fiber tracing data showed that the corticospinal tract fibers were found only in the unaffected hemisphere but not in the affected hemisphere. Show more

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 5-6, pp. 325-329, 2005

Authors: Nicotra, Alessia | Catley, Maria | Ellaway, Peter H. | Mathias, Christopher J.

Article Type: Research Article

Abstract: Purpose. Sympathetic sudomotor function in chronic spinal cord injury (SCI) has been evaluated to determine if recording the sympathetic skin response (SSR) provides evidence of integrity of the spinal component of the sympathetic pathways. Methods. Thirty subjects with chronic SCI and 15 healthy normal subjects were studied. The SSR was elicited using two physiological (auditory and inspiratory gasp) stimuli. In addition, electrical (median and peroneal nerve) stimulation was also performed. Recordings were made from …palmar and plantar sites. Results. Palmar and plantar SSRs could be readily elicited in all control subjects by all stimuli. In the majority of SCI subjects, the presence or absence of the SSR was related to the American Spinal Injury Association (ASIA) impairment scale, which incorporates only motor and sensory assessments. The exceptions indicated preserved (or damaged) sympathetic spinal cord pathways. Conclusions. We conclude that the SSR, using either physiological or electrical stimuli, may be a reliable, non-invasive method of determining integrity of sympathetic cholinergic pathways in SCI, with potential for monitoring the effects of intervention and spinal repair. Show more

Keywords: Sympathetic skin response, spinal cord injury, sympathetic pathways

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 5-6, pp. 331-339, 2005

Authors: Boran, Burak O. | Colak, Ahmet | Kutlay, Murat

Article Type: Research Article

Abstract: Purpose: Erythropoietin is a hematopoietic growth factor. It is also involved in neurodevelopment and neuroprotection. The purpose of this study was to evaluate the effectiveness of erythropoietin in enhancing the neurological recovery following experimental spinal cord injury. Methods: Rats were randomly divided into 4 groups. Group 1 received only laminectomy. Group 2, 3, and 4 have undergone a spinal contusion injury of 50 gr/cm. Group 2 received no medication. Group 3 received 30 mg/kg …methylprednisolone. Group 4 received 5000 IU/kg recombinant human erythropoietin. Following injury, neurological recovery was evaluated for 14 days, using a swimming test. Results: At day 1, there was no difference between mean motor scores of group 2, 3, and 4. Following day 1, rats in group 4 exhibited a marked improvement in motor score, and this was maintained throughout the study. When compared to group 2, mean motor score of group 4 was significantly higher at day 4, 7, 10, and 14. When compared to group 3, mean motor score of group 4 was significantly higher at day 7, 10, and 14. Conclusion: These findings suggest that erythropoietin enhances neurological recovery following spinal cord injury and it seems to be more effective than methylprednisolone at the given doses. Show more

Keywords: Erythropoietin, neuroprotection, spinal cord injury

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 5-6, pp. 341-345, 2005

Authors: Mert, Tufan | Gunay, Ismail | Polat, Sait

Article Type: Research Article

Abstract: Purpose: Nerve crush injury results in the incapability to maintain conduction of an impulse. Disruption in the myelin sheath causes very important changes in the activities of ion channels. Therefore, crushed and intact sciatic nerves were researched with both histological and electrophysiological methods in this study. Methods: Electron and light microscopy for histological examinations, a sucrose-gap recording techniques for electrophysiological examinations were used. 4-aminopyridine (4-AP) and Tetraethylammonium (TEA) were used …to functional separation of the fast and slow K^+ channels. Results: The number of damaged myelinated nerve fiber was counted as 750 ± 3.5. Lamellar separation and disruption in myelin sheath was frequently observed in these fibers. Conduction velocity of crushed nerves (19 ± 2 m/s) was half of the intact nerves. The relationship between equally spaced interstimulus interval and their responses demonstrated that 4-AP and 4-AP plus TEA have more pronounced effects on crushed nerves than on intact nerves. After 4-AP, TEA application caused an efficiently depolarization in the membrane potential. Conclusions: The effects of 4-AP and 4-AP plus TEA suggest the involvement of slow and fast K^+ channels and slow Na^+ currents in membrane potential and action potential repolarization. Minimal myelin damage may significantly influence the subsequent impulse generation and the patterning of action potential activity. Show more

Keywords: Crush injury, action potential, conduction velocity, sodium channels, potassium channels

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 5-6, pp. 347-354, 2005

Authors: Rong, Ling Ling | Gooch, Clifton | Szabolcs, Mattias | Herold, Kevan C. | Lalla, Evanthia | Hays, Arthur P. | Yan, Shi Fang | Yan, Shirley Shi Du | Schmidt, Ann Marie

Article Type: Research Article

Abstract: The Receptor for Advanced Glycation End Products (RAGE) is a multiligand member of the immunoglobulin superfamily. RAGE interacts with AGEs, the products of nonenzymatic glycation/oxidation of proteins and lipids that accumulate in diverse settings, such as diabetes, inflammation, renal failure, pro-oxidant states and natural aging. In addition, RAGE is also a receptor for amyloid-β peptide and β-sheet fibril species. Recent studies underscore the premise that RAGE interacts with pro-inflammatory molecules, including S100/calgranulins …and amphoterin, the latter also known as high mobility group box 1 (HMGB1). In chronic neurodegenerative disorders as well as in nerve tissue upon acute injury, evidence points to upregulation of both RAGE and these ligand families. In this review, we will discuss the implications of transient/self-limited upregulation of RAGE and its ligands, vs sustained/chronic upregulation of this axis in neurodegeneration vs repair in both the central and peripheral nervous systems. Experimental evidence supports the premise that RAGE bears both homeostatic and injurious properties in the nervous system, thereby highlighting "yin/yang" features of this receptor and its ligand families. Show more

Keywords: Receptor, ligands, nerve crush, neurodegeneration, regeneration

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 5-6, pp. 355-365, 2005

Authors: Abrams, Matthew | Widenfalk, Johan

Article Type: Research Article

Abstract: Purpose: To present a general review of experimental strategies used to improve functional outcome after peripheral nerve injury. In order to understand the mechanisms behind the strategies, the process of nerve healing after injury is described briefly and each strategy is described in its context. Since the functional outcome is not solely determined by nerve regeneration but by a number of different factors, we have also chosen to cover many other important topics. Methods: …Literature review. Results: Review article. Conclusions: Functional outcome after peripheral nerve injury is often poor and sometimes associated with neuropathic pain. Therapeutic intervention can be carried out at different levels and we attempt to place the different strategies and target molecules, in the context of the nerve healing process. The most obvious interventions are perhaps to minimize cell death and enhance regeneration across the lesion gap. Others, which are more difficult, may be to limit neuropathic pain, improve target finding and cortical reorganization, counteract effects of prolonged denervation/axotomy, and reduce electrical conduction block at the scar formation. Although clinical outcome is often poor at present, recent preclinical research provides several promising approaches and new target molecules for therapeutic intervention, such as neurotrophic factor (GDNF and ARTN) treatment of neuropathic pain, manipulation of the small Rho GTPases (Rac, Rho, Cdc42, Tc10), lipid raft manipulation, gene silencing with DNA enzyme and siRNA. In addition, recent research involving high throughput screening of gene expression (microarray) after nerve injury encourages the discoveries of new possible target molecules. Show more

Keywords: Nerve regeneration, fibrin glue, proteases, axon guidance, schwann cell, Rho GTPases, neurotrophic factors, lipid raft

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 5-6, pp. 367-382, 2005