Restorative Neurology and Neuroscience - Volume 29, issue 4

Authors: Shear, Deborah A. | Tate, Ciara C. | Tate, Matthew C. | Archer, David R. | LaPlaca, Michelle C. | Stein, Donald G. | Dunbar, Gary L.

Article Type: Research Article

Abstract: Purpose: Recent work indicates that transplanted neural stem cells (NSCs) can survive, migrate to the injury site, and facilitate recovery from traumatic brain injury (TBI). The present study manipulated timing and location of NSC transplants following controlled cortical impact injury (CCI) in mice to determine optimal transplant conditions. Methods: In Experiment 1 (timing), NSCs (E14.5 mouse) were injected into the host striatum, ipsilateral to the injury, at 2, 7, or 14 days. In Experiment 2 (location), NSCs or vehicle were injected into the mouse striatum (7 days post-CCI) either ipsilateral or contralateral to the injury and cognitive and motor abilities …were assessed from weeks 1–8 post-transplant. Histological measures of NSC survival, migration, and differentiation were taken at 6 and 8 weeks post-transplant. Results: The results demonstrate that: (1) 2–7 days post-injury is the optimal time-range for delivering NSCs; (2) time of transplantation does not affect short-term phenotypic differentiation; (3) transplant location affects survival, migration, phenotype, and functional efficacy; and (4) NSC-mediated functional recovery is not contingent upon NSC migration or phenotypic differentiation. Conclusions: These findings provide further support for the idea that mechanisms other than the replacement of damaged neurons or glia, such as NSC-induced increases in protective neurotrophic factors, may be responsible for the functional recovery observed in this model of TBI. Show more

Keywords: neural stem cells, traumatic brain injury, motor recovery, spatial learning and memory, stem cell survival and migration, CNS repair

DOI: 10.3233/RNN-2011-0593

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 4, pp. 215-225, 2011

Authors: Ozsoy, Umut | Demirel, Bahadir Murat | Hizay, Arzu | Ozsoy, Ozlem | Ankerne, Janina | Angelova, Srebrina | Sarikcioglu, Levent | Ucar, Yasar | Angelov, Doychin N.

Article Type: Research Article

Abstract: Purpose: The outcome of severe peripheral nerve injuries requiring surgical repair (transection and suture) is usually poor. Recent work suggests that direct suture of nerves increases collagen production and provides unfavourable conditions for a proper axonal regrowth. We tested whether entubulation of the hypoglossal nerve into a Y-tube conduit connecting it with the zygomatic and buccal facial nerve branches would improve axonal pathfinding at the lesion site, quality of muscle reinnervation and recovery of vibrissal whisking. Methods: For hypoglossal-facial anastomosis (HFA) over a Y-tube (HFA-Y-tube) the proximal stump of the hypoglossal nerve was entubulated and sutured into the long arm …of a Y-tube (isogeneic abdominal aorta with its bifurcation). The zygomatic and buccal facial branches were entubulated and sutured to the short arms of the Y-tube. Restoration of vibrissal motor performance, degree of collateral axonal branching at the lesion site and quality of neuro-muscular junction (NMJ) reinnervation were compared to animals receiving HFA-Coaptation (no entubulation) after 4 months. Results: HFA-Y-tube reduced collateral axonal branching. However it failed to reduce the proportion of polyinnervated NMJ and did not improve functional outcome when compared to HFA-Coaptation. Conclusion: Elimination of compression by tightly opposed nerve fragments improved axonal pathfinding. However, biometric analysis of vibrissae movements did not show positive effects suggesting that polyneuronal reinnervation - rather than collateral branching – may be the critical limiting factor. Since polyinnervation of muscle fibers is activity-dependent and can be manipulated, the present findings raise hopes that clinically feasible and effective therapies after HFA could be soon designed and tested. Show more

Keywords: Motoneuron, nerve repair, facial nerve, hypoglossal nerve, entubulation, functional recovery

DOI: 10.3233/RNN-2011-0594

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 4, pp. 227-242, 2011

Authors: del Barco, Diana García | Montero, Enrique | Coro-Antich, Rosa M. | Brown, Enma | Suarez-Alba, José | Lopez, Laura | Subirós, Nelvys | Berlanga, Jorge

Article Type: Research Article

Abstract: Purpose: Multiple sclerosis is a complex and devastating autoimmune disease of the central nervous system. Up to now, a constellation of candidate drugs have been evaluated with no major success. Experimental Autoimmune Encephalitis (EAE) is the animal counterpart that reproduces critical features of the human MS process. The aim of the present work is to study a possible therapeutic effect of epidermal growth factor (EGF) and growth hormone releasing peptide-6 (GHRP6 coadministration in mild and severe EAE. Methods: Mild and severe forms of EAE were generated immunizing rats and mice with xenogeneic spinal cord homogenate and with the encephalitogenic …peptide MOGp35–35 , respectively. EGF and GHRP6 alone or combined were administered in therapeutic and prophylactic schedules. A clinical score was established to follow-up the animals during the disease period. Malondialdehyde (MDA) serum concentration and insulin like growth factor-1 (IGF-1) relative level from brain tissue were determined. Results: Only the combined EGF+GHRP6 therapy reduced the clinical score in mild as well in severe EAE forms. The combination also improved the survival rate in nearly 100% of the severe EAE animals. In addition to these effects, there was an increase in the brain IGF-1 transcript and a decrease of serum MDA. Conclusions: EGF+GHRP6 proved to be effective in improving the natural course of both mild and severe EAE. Accordingly, the treatment reduces inflammatory infiltration and microvascular damage, which may be associated to the attenuation of the lipid peroxidation process and the transcriptional enhancement of IGF-1, a major pro-survival factor for brain cells. Show more

Keywords: EAE, multiple sclerosis therapy, EGF, GHRP\(_{\rm{6}}\), IGF-1

DOI: 10.3233/RNN-2011-0595

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 4, pp. 243-252, 2011

Authors: Hassa, Thomas | Schoenfeld, Mircea Ariel | Dettmers, Christian | Stoppel, Christian Michael | Weiller, Cornelius | Lange, Rüdiger

Article Type: Research Article

Abstract: Purpose: Recent evidence from neuroimaging studies using visual tasks suggests that the right superior parietal cortex plays a pivotal role for the recovery of neglect. Importantly, neglect-related deficits are not limited to the visual system and have a rather multimodal nature. We employed somatosensory stimulation in patients with neglect in order to analyze activity changes in networks that are presumably associated with this condition. Methods: Eleven chronic neglect patients with right hemispherical stroke were investigated with a fMRI paradigm in which the affected and unaffected hand were passively moved. Results: Brain activation was correlated with the performance in clinical neglect …tests. Significant positive correlations with brain activation were found for the lesion duration, the performance in bells and letter cancellation tests and the line bisection test. These activated areas formed a distributed pattern in the right superior parietal cortex. Conclusions: The results suggest a shared representation of visual and somatosensory networks in the right superior parietal cortex in patients with right hemispherical strokes and neglect. The spatial pattern of activity in the superior parietal cortex points out to a different representation of changes related to lesion duration and neglect. Show more

Keywords: Neglect, fMRI, recovery of function, somatosensory processing, passive movement, superior parietal lobe

DOI: 10.3233/RNN-2011-596

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 4, pp. 253-263, 2011

Authors: Lin, Yi-Lo | Kuo, Huai-Sheng | Lo, Ming-Jei | Tsai, May-Jywan | Lee, Meng-Jen | Huang, Wen-Cheng | Kuo, Wen-Chun | Shih, Yang-Hsin | Cheng, Henrich | Huang, Ming-Chao

Article Type: Research Article

Abstract: Purpose: Nerve root traction injuries induce spinal cord inflammation and lead to neuronal death within days. In the present study, we examined the inflammatory response one week after multiple cervical root transections. Methods: In the transection group, the left cervical roots (C6-8) of rats were cut at the spinal cord junction. In the repair group, transected roots were repaired with nerve grafts and the subsequent application of aFGF and fibrin glue. A sham group had nerve roots exposed without transection. Mechanical allodynia and spinal glial responses were evaluated. Results: Allodynia did not differ between the treatment groups on day 2. …Rats with transected spinal nerve roots had significantly more allodynia by 7 days, which was associated with IL-1β expression in dorsal and ventral horn astrocytes, and microglia activation. Repair of nerve roots with autologous intercostal nerve grafts and FGF in fibrin glue attenuated the allodynia, reduced IL-1β expression in astroctyes and reduced microglia activation, along with a significant increase in arginase I expression. Conclusion: This study demonstrated a correlation between an increased number of IL-1β-positive astrocytes and the development of allodynia. Our treatment significantly decreased IL-1β-positive astrocytes, thus preventing the occurrence of neuropathic pain following multiple cervical root injuries. Show more

DOI: 10.3233/RNN-2011-0597

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 4, pp. 265-274, 2011

Authors: Onifer, Stephen M. | Zhang, Oliver | Whitnel-Smith, Laura K. | Raza, Kashif | O'Dell, Christopher R. | Lyttle, Travis S. | Rabchevsky, Alexander G. | Kitzman, Patrick H. | Burke, Darlene A.

Article Type: Research Article

Abstract: Purpose: Using the horizontal ladder task, we examined some issues that need to be resolved before task-specific rehabilitative training can be employed clinically for the frequent contusive spinal cord injury (SCI). We hypothesized that improving recovery in task performance after contusive thoracic SCI requires frequent re-training and initiating the re-training early during spontaneous recovery. Methods: Contusive SCI was produced at the adult female Sprague Dawley rat T10 vertebra. Task re-training was initiated one week later when occasional weight-supported plantar steps were taken overground (n = 8). It consisted of 2 repetitions each day, 5 days each week, for 3 weeks. …Task performance and overground locomotion were assessed weekly. Neurotransmission through the SCI ventrolateral funiculus was examined. SCI morphometry was determined. Results: Re-training did not improve task performance recovery compared to untrained Controls (n = 7). Untrained overground locomotion and neurotransmission through the SCI did not change. Lesion area at the injury epicenter as a percentage of the total spinal cord area as well as total tissue, lesion, and spared tissue, white matter, or gray matter volumes did not differ. Conclusions: For the horizontal ladder task after contusive thoracic SCI, earlier re-training sessions with more repetitions and critical neural circuitry may be necessary to engender a rehabilitation effect. Show more

Keywords: Spinal cord injury, rehabilitation, re-training, horizontal ladder, locomotion, transcranial magnetic motor evoked potentials

DOI: 10.3233/RNN-2011-598

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 4, pp. 275-286, 2011