Restorative Neurology and Neuroscience - Volume 27, issue 6

Authors: Sabel, B.A. | Matzke, S. | Prilloff, S.

Article Type: Research Article

Abstract: The journal Restorative Neurology and Neuroscience (RNN) now celebrates its 20th anniversary. Since 1989 RNN has published scientific findings in the emerging fields of brain plasticity, repair and rehabilitation via original scientific publications and review papers in basic research (animal experiments, in vitro studies) and clinical science. During the last decade RNN had a steady progress in reference value and scientific impact, reaching an ISI-impact factor of 1.978 (2008) and has published a total of 717 …papers. The journal's success can be explained by different factors: (1) neuroplasticity, regeneration, recovery and rehabilitation have developed to main stream subjects with a worldwide increase in the number of publications and their citation rate, (2) RNN has published numerous special issues which summarize the work of leading experts in specialized sub-fields, (3) a dedicated, highly qualified editorial board, and (4) the quality of papers submitted to RNN has increased over time. RNN has now become a visible and leading source of original scientific information in the space of brain plasticity, rehabilitation and repair. Show more

DOI: 10.3233/RNN-2009-0545

Citation: Restorative Neurology and Neuroscience, vol. 27, no. 6, pp. 579-587, 2009

Authors: Stein, Donald G.

Article Type: Research Article

DOI: 10.3233/RNN-2009-0546

Citation: Restorative Neurology and Neuroscience, vol. 27, no. 6, pp. 589-590, 2009

Authors: Tass, P.A. | Hauptmann, C.

Article Type: Research Article

Abstract: Purpose: Different stimulation techniques are introduced which specifically modulate the slow synaptic dynamics in a neuronal network model of the subthalamic nucleus with activity dependent synaptic plasticity. Methods: A modeling approach is utilized to investigate the effects of the different stimulation techniques. In particular, the short-term and long-term outcome is studied in a mathematical model for a population of bursting STN neurons subject to synaptic plasticity with symmetric spike timing characteristics. In our mathematical …model in the absence of stimulation synchronized network states with strong connectivity (modeling disease states) as well as desynchronized states with weak connectivity (modeling healthy states) are stable. Results: We demonstrate that different stimulation techniques induce an anti-kindling by shifting the target population to a weakly connected, desynchronized state. Intriguingly, long-term anti-kindling can even be achieved although during stimulus delivery the neuronal synchrony hardly decreases or even slightly increases. The therapeutic index and the impact of inhibition, calculated to compare the different stimulation techniques, indicate that coordinated rest stimulation might be particularly robust and reliable. Conclusions: The presented stimulation strategies and the results of our modeling study might have strong implications in the context of deep brain stimulation. Show more

Keywords: Deep brain stimulation, desynchronization, plasticity, therapeutic stimulation, slow synaptic dynamics

DOI: 10.3233/RNN-2009-0484

Citation: Restorative Neurology and Neuroscience, vol. 27, no. 6, pp. 591-611, 2009

Authors: Khaing, Zin Z. | Roberts, James L.

Article Type: Research Article

Abstract: Purpose: Stem cells and progenitor cells in the central nervous system may have potential for therapeutic use in patients with degenerative diseases or after injury. Neural precursor cells can be grown in culture in the presence of mitogens as aggregates termed neurospheres (NSs), as a source of proliferating progenitor cells. Withdrawal of mitogen and allowing the NSs to adhere to a substrate is the conventional way to study the differentiation potential of the progenitor cells propagated …in NSs form. Here we asked if differentiation occurs within NSs cultured in the normal manner, in the presence of mitogen. Methods: We used non-passaged NSs derived from E13.5 mouse ventral mesencephalon. Results: The NSs contained not only progenitor cells but also phenotypically-differentiated neurons and glia, in the presence of mitogen. Extracellular matrix molecules (fibronectin, laminin and collagen type IV) were also detected within these NSs, which may aid in the differentiation of progenitors inside the NSs. The cell types within NSs were also organized in a way that the differentiated cells were found in the inner cell mass while progenitors were found in the outer region. Additionally, the proportion of differentiated cell types within the NSs was also affected by exposure to different mitogens. Moreover, when placed together in to co-culture, dissociated embryonic striatal and mesencephalic cells aggregated spontaneously to form mixed NSs, enhancing the eventual differentiation into dopaminergic neurons from progenitors within these NSs. Conclusion: Therefore, the NSs contained progenitor cells and differentiated neurons and glial cells. In addition, NS culture system can be used to study cellular differentiation in vitro in non-adherent conditions. Show more

Keywords: Ventral mesencephalon, neurosperes, co-culturing, differentiation

DOI: 10.3233/RNN-2009-0486

Citation: Restorative Neurology and Neuroscience, vol. 27, no. 6, pp. 613-622, 2009

Authors: Ness, Lanitia L. | Field-Fote, Edelle C.

Article Type: Research Article

Abstract: Purpose: Individuals with spinal cord injury (SCI) often have involuntary, reflex-evoked muscle activity resulting in spasticity. Vibration may modulate reflex activity thereby decreasing spasticity. This study suggests feasibility of using whole-body vibration (WBV) to decrease quadriceps spasticity in individuals with SCI. Methods: Participants were individuals (n=16) with spastic quadriceps hypertonia due to chronic SCI (> 1 year). Quadriceps spasticity was measured by gravity-provoked stretch (Pendulum Test) before (initial) and after …(final) a 3 day/week, 12-session WBV intervention. In addition, differences between immediate (immediate post-WBV) and delayed (delayed post-WBV) within-session effects were quantified. Finally, we assessed response differences between subjects who did and those who did not use antispastic agents. Results: There was a significant reduction in quadriceps spasticity after participation in a WBV intervention that persisted for at least eight days. Within a WBV session, spasticity was reduced in the delayed post-WBV test compared to the immediate post-WBV test. The WBV intervention was associated with similar changes in quadriceps spasticity in subjects who did and those who did not use antispastic agents. Conclusions: Vibration may be a useful adjunct to training in those with spasticity. Future studies should directly compare the antispastic effects of vibration to those of antispastic agents. Show more

Keywords: Spinal reflex, human movement system, rehabilitation, stretch reflex, reflex modulation, Pendulum Test

DOI: 10.3233/RNN-2009-0487

Citation: Restorative Neurology and Neuroscience, vol. 27, no. 6, pp. 623-633, 2009

Authors: Sharma, Nijee | Coughlin, Lisa | Porter, Ryan G. | Tanzer, Lisa | Wurster, Robert D. | Marzo, Sam J. | Jones, Kathryn J. | Foecking, Eileen M.

Article Type: Research Article

Abstract: Purpose: The neurotherapeutic effects of nerve electrical stimulation and gonadal steroids have independently been demonstrated. The purpose of this study was to investigate the therapeutic potential of a combinatorial treatment strategy of electrical stimulation and gonadal steroids on peripheral nerve regeneration. Methods: Following a facial nerve crush axotomy in gonadectomized adult male rats, testosterone propionate (TP), dihydrotestosterone (DHT), or estradiol (E_{2} ) was systemically administered with/without daily electrical stimulation …of the proximal nerve stump. Facial nerve outgrowth was assessed at 4 and 7 days post-axotomy using radioactive labeling. Results: Administration of electrical stimulation alone reduced the estimated delay in sprout formation but failed to accelerate the overall regeneration rate. Conversely, TP treatment alone accelerated the regeneration rate by ∼10% but had no effect on the sprouting delay. Combining TP with electrical stimulation, however, maintained the enhanced rate and reduced the sprouting delay. DHT treatment alone failed to alter the regeneration rate but combining it with electrical stimulation increased the rate by 10%. E_{2} treatment alone increased the regeneration rate by ∼5% but with electrical stimulation, there was no additional effect. Conclusions: Electrical stimulation and gonadal steroids differentially enhanced regenerative properties. TP, an aromatizable androgen, augmented regeneration most, suggesting a synergism between androgenic and estrogenic effects. Therapeutically, combining electrical stimulation with gonadal steroids may boost regenerative properties more than the use of either treatment alone. Show more

Keywords: Peripheral nerve injury, regeneration, electrical stimulation, gonadal steroids

DOI: 10.3233/RNN-2009-0489

Citation: Restorative Neurology and Neuroscience, vol. 27, no. 6, pp. 635-646, 2009

Authors: Kang, Eun Kyoung | Baek, Min Jae | Kim, SangYun | Paik, Nam-Jong

Article Type: Research Article

Abstract: Purpose: Attention decline after stroke is common and hampers the rehabilitation process, and non-invasive transcranial direct current stimulation (tDCS) has the potential to elicit behavioral changes by modulating cortical excitability. The authors tested the hypothesis that a single session of non-invasive cortical stimulation with excitatory anodal tDCS applied to the left dorsolateral prefrontal cortex (DLPFC) can improve attention in stroke patients. Methods: Ten patients with post-stroke cognitive decline (MMSE ⩽ …25) and 10 age-matched healthy controls participated in this double blind, sham-controlled, crossover study involving the administration of real (2 mA for 20 min) or sham stimulation (2 mA for 1 min) to the left DLPFC. Attention was measured using a computerized Go/No-Go test before and after intervention. Improvements in accuracy and speed after stimulation relative to baseline were compared for real and sham stimulations. Results: In healthy controls, no significant improvement in Go/No-Go test was observed after either real or sham stimulation. However, in stroke patients, tDCS led to a significant improvement in response accuracy at 1 hour post-stimulation relative to baseline, and this improvement was maintained until 3 hours post-stimulation (P< 0.05), whereas sham stimulation did not lead to a significant improvement in response accuracy (P> 0.05). Changes in reaction times were comparable for the two stimulations (P> 0.05). Conclusion: Non invasive anodal tDCS applied to the left DLPFC was found to improve attention versus sham stimulation in stroke patients, which suggests that non-invasive cortical intervention could potentially be used during rehabilitative training to improve attention. Show more

Keywords: Attention, cognition, stroke, cortical stimulation, tDCS

DOI: 10.3233/RNN-2009-0514

Citation: Restorative Neurology and Neuroscience, vol. 27, no. 6, pp. 647-652, 2009

Authors: Sinis, Nektarios | Di Scipio, Frederica | Schönle, Phillip | Werdin, Frank | Kraus, Armin | Koopmanns, Guido | Masanneck, Carmen | Hermanns, Susanne | Danker, Timm | Guenther, Elke | Haerle, Max | Schaller, Hans-Eberhard | Geuna, Stefano | Mueller, Hans-Werner

Article Type: Research Article

Abstract: Purpose: The improvement of regeneration and functional recovery after peripheral nerve injury is a major challenge in neurosurgery. Although microsurgical techniques for nerve reconstruction have seen great advancements over the last years, the clinical outcome with patients is often unsatisfactory. The aim of the present study was to investigate if administration of the iron chelator Deferroxamine (DFO), can improve postoperative outcome in the rat median nerve reconstruction model. Methods: After complete transection, the right …median nerve was repaired by end-to-end neurorrhaphy. The suture site was wrapped by a 1-cm-long external jugular vein segment, either empty or filled with DFO-loaded lipid particles (Perineurin© or with a vehicle (unloaded lipid particles) alone. Functional testing was carried out weekly by means of the grasping test. At the time of withdrawal, 12 weeks post-operatively, muscle tropism recovery was assessed by weighing flexor digitorum sublimis muscle that is innervated by the median nerve only. Before harvesting of the nerve specimens electrophysiological analyses were performed with measuring the latency, the threshold and the conduction velocity. Finally, the repaired nerves were withdrawn for immunocytochemistry with a neurofilament antibody and axon quantitative morphology. Results: The comparison between the groups showed that intraoperative application of the DFO-loaded lipid particles at the neurorrhaphy site led to a significant increase in the density of regenerating axons as well as to an accelerated recovery of both muscle tropism and motor function. The electrophysiological results demonstrated a decrease of the threshold, a lower latency, and a higher conduction velocity in the Perineurin©-treated animals. Conclusions: The results of the present study suggest that local administration of Perineurin© might have a therapeutic potential for improving the postoperative outcome after microsurgical nerve reconstruction in patients. Show more

Keywords: Primary nerve suture, iron chelator, nerve regeneration, median nerve

DOI: 10.3233/RNN-2009-0517

Citation: Restorative Neurology and Neuroscience, vol. 27, no. 6, pp. 653-664, 2009

Authors: Luukkainen-Markkula, R. | Tarkka, I.M. | Pitkänen, K. | Sivenius, J. | Hämäläinen, H.

Article Type: Research Article

Abstract: Purpose: Hemispatial neglect, a failure to orient to the contralateral side of the lesion, is a disabling disorder after stroke. Previously arm activation combined with visual training or visual scanning training were found effective in rehabilitation of hemispatial neglect. The aim of this study was to determine whether left arm activation alone could be sufficient to produce a long lasting amelioration of neglect comparable to the effect obtained with traditional visual scanning training. Methods: …Twelve neglect patients less than six months from stroke were randomized either into 20–30 hours of left arm activation training or 10 hours of traditional visual scanning training as a part of a comprehensive rehabilitation program. All patients received 48~hours of therapy during the 3-week rehabilitation. Results: Visual neglect of the arm activation group recovered significantly in the conventional subtests of the Behavioural Inattention Test both post-rehabilitation and at 6-months follow-up. The improvement of the visual scanning training group was almost significant at the end of the rehabilitation and significant by the follow-up. The behavioural neglect observed in the Catherine Bergego Scale was alleviated nearly significantly at the post-rehabilitation in both groups. The effect was maintained in the arm activation group at 6-months. Conlusion: The arm activation training appears beneficial even without supplementary visual neglect rehabilitation, although the traditional visual scanning training may have further effects in cognition. Show more

DOI: 10.3233/RNN-2009-0520

Citation: Restorative Neurology and Neuroscience, vol. 27, no. 6, pp. 665-674, 2009

Authors: Barzel, Anne | Liepert, Joachim | Haevernick, Kerstin | Eisele, Marion | Ketels, Gesche | Rijntjes, Michel | van den Bussche, Hendrik

Article Type: Research Article

Abstract: Several studies showed that Constraint-Induced Movement Therapy (CIMT) leads to a lasting improvement of upper extremity function in chronic stroke patients. The original technique includes an intensive 2-week program with 6 hours of daily physiotherapy. Due to high expenses it is difficult to implement this concept in outpatient care. Purpose: The objective of this study was to evaluate the effects of a 4-week homebased CIMT program among chronic stroke patients and to compare them …with a 2-week CIMT program, based on the original technique. Methods: Seven adults with chronic stroke completed a newly developed variant of CIMT, performed at patients' homes (group1, CIMThome), supervised by an instructed family member, constraint of unaffected hand for a target of 60% of waking hours. The intervention was analysed with pre-, post-treatment and 6-month follow-up measurements. Effects on improvement in upper extremity function were compared with patients treated according to the original protocol (group2, CIMTclassic), supervised by a physiotherapist, constraint of unaffected hand for a target of 90% of waking hours. Results: Patients from both groups showed almost identical improvement of their motor function according to scores on the Wolf Motor Function Test (WMFT) and the Motor Activity Log (MAL) immediately after the treatment period as well as at follow-up after 6 months. Conclusions: Our study suggests that CIMThome is not only feasible but also as effective as CIMTclassic. This finding should be replicated in a larger prospective randomized trial to perform a non-inferiority analysis. Show more

Keywords: Stroke, rehabilitation, constraint-Induced movement therapy

DOI: 10.3233/RNN-2009-0524

Citation: Restorative Neurology and Neuroscience, vol. 27, no. 6, pp. 675-682, 2009