Restorative Neurology and Neuroscience - Volume 33, issue 1

Authors: Nardai, Sándor | Dobolyi, Arpád | Pál, Gabriella | Skopál, Judit | Pintér, Nándor | Lakatos, Kinga | Merkely, Béla | Nagy, Zoltán

Article Type: Research Article

Abstract: Purpose: Our experiments aimed at exploring potential neurorestorative mechanisms of selegiline, a compound routinely used in the treatment of Parkinson's disease and previously shown to improve the functional recovery of stroke patients. Methods: Selegiline was administered continuously via osmotic mini-pumps between 48 and 216 hours following middle cerebral artery occlusion (MCAO) in rats. Twenty-four hours before sacrifice, the animals underwent magnetic resonance imaging (MRI). After decapitation, the peri-infarct region was dissected to perform a TAQMAN array gene expression study, and brains were fixed for immunolabeling. Results: In addition to the previously known induction of anti-apoptosis genes, selegiline significantly increased the …mRNA level of Notch 1 receptor and its ligand Jagged 1. Immunohistochemistry demonstrated elevated Notch 1 and Jagged 1 immunoreactivities in the peri-infarct region. Double labeling with glial markers revealed that both Notch 1 and Jagged 1 were expressed in astrocytes but not in microglia. MRI examination indicated significantly reduced edema in selegiline-treated rats compared to control MCAO rats, and increased capillary network density was found in the peri-infarct region of the selegiline-treated animals. Conclusion: Our results suggest that selegiline treatment enhances Notch-Jagged signaling in astrocytes, reduces peri-lesional edema and potentially helps preserve the capillary network following focal ischemia. Show more

Keywords: Notch 1 and Jagged 1 induction, mRNA expression by TAQMAN array, middle cerebral artery occlusion, neuroprotection in stroke, astrocyte activation in reactive gliosis, edema

DOI: 10.3233/RNN-140420

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 1, pp. 1-14, 2015

Authors: Föcker, Julia | Hölig, Cordula | Best, Anna | Röder, Brigitte

Article Type: Research Article

Abstract: Purpose: Intra- and crossmodal neuroplasticity have been reported to underlie superior voice processing skills in congenitally blind individuals. The present study used event-related potentials (ERPs) in order to test if such compensatory plasticity is limited to the developing brain. Methods: Late blind individuals were compared to sighted controls in their ability to identify human voices. A priming paradigm was employed in which two successive voices (S1, S2) of the same (person-congruent) or different speakers (person-incongruent) were presented. Participants made an old-young decision on the S2. Results: In both groups ERPs to the auditory S2 were more negative in person-incongruent than …in person-congruent trials between 200–300 ms. A topographic analysis suggested a more posteriorly shifted distribution of the Person Match effect (person-incongruent minus person-congruent trials) in late blind individuals compared to sighted controls. Conclusion: In contrast to congenitally blind individuals, late blind individuals did not show an early Person Match effect in the time range of the N1, suggesting that crossmodal compensation is mediated by later processing steps rather than by changes at early perceptual levels. Show more

Keywords: Late blind, sensory deprivation, plasticity, voice, person recognition, event related potentials

DOI: 10.3233/RNN-140406

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 1, pp. 15-30, 2015

Authors: Borich, Michael R. | Neva, Jason L. | Boyd, Lara A.

Article Type: Research Article

Abstract: Purpose: Rehabilitation interventions need to be optimized to maximize therapeutic effects and minimize stroke-related disability. However, a comprehensive understanding of the neural substrates underlying recovery is lacking. The purpose of this study was to investigate relationships between brain anatomy, physiology and hand motor function in individuals with chronic stroke. Methods: Transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) approaches were used to evaluate cortical excitability and brain structural morphometry in individuals with chronic stroke. Hemispheric differences and relationships between these measures and hand dexterity were evaluated. Results: Hemispheric differences were observed for TMS and MRI measures. Bilateral hand dexterity …correlated with TMS resting motor threshold and precentral gyral thickness. Transcallosal inhibition across hemispheres was positively associated with midcallosal white matter volume. Regression modeling results demonstrated that combining TMS and MRI measures predicted unique amounts of variance in hand dexterity. Conclusions: Results confirm and extend findings showing differences in brain structure and function after stroke. Results suggested a structure-function relationship underlying interhemispheric connectivity in chronic stroke. The utility of combined TMS and MRI measures to predict motor function can be used in future investigations to aid identifying optimal biomarkers of stroke recovery to predict response to rehabilitation to maximize treatment outcomes. Show more

Keywords: Stroke, transcranial magnetic stimulation, magnetic resonance imaging, cortical excitability, morphometry, rehabilitation, hand dexterity

DOI: 10.3233/RNN-140425

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 1, pp. 31-42, 2015

Authors: de Almeida, Fernanda Martins | Marques, Suelen Adriani | Ramalho, Bruna dos Santos | Massoto, Tamires Braga | Martinez, Ana Maria Blanco

Article Type: Research Article

Abstract: Purpose: Despite substantial advances in surgical care and rehabilitation, the consequences of spinal cord injury (SCI) continue to present major challenges. Here we investigate whether transplantation of mesenchymal stem cells (MSCs) in mice during the chronic stage of SCI has benefits in terms of morphological and functional outcomes. Methods: Mice were subjected to laminectomy at the T9 level, followed by a 1 minute spinal cord compression with a vascular clip. Four weeks later, 8 × 105 MSCs obtained from GFP mice were injected into the injury site. After eight weeks the analyses were performed. Results: The spinal cords of …MSC-treated animals exhibited better white-matter preservation, greater numbers of fibers, higher levels of trophic factor expression, and better ultrastructural tissue organization. Furthermore, transplanted MSCs were not immunoreactive for neural markers, indicating that these cells mediate functional recovery through a paracrine effect, rather than by transforming into and replacing damaged glia in the spinal cord. MSC-treated mice also showed better functional improvement than control animals. Conclusion: We conclude that MSC-based cell therapy, even when applied during the chronic phase of SCI, leads to changes in a number of structural and functional parameters, all of which indicate improved recovery. Show more

Keywords: Spinal cord injury, cell therapy, functional recovery, morphological analysis

DOI: 10.3233/RNN-140431

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 1, pp. 43-55, 2015

Authors: Duret, Christophe | Hutin, Emilie | Lehenaff, Laurent | Gracies, Jean-Michel

Article Type: Research Article

Abstract: Purpose: Upper limb robot-assisted rehabilitation is a highly intensive therapy, mainly recommended after stroke. Whether robotic therapy is suitable for subacute patients with severe impairments including cognitive disorders is unknown. This retrospective study explored factors impacting on motor performance achieved in a 16-session robotic training combined with standard rehabilitation. Methods: Seventeen subacute inpatients (age 53 ± 18; 49 ± 26 days post-stroke) were assessed at baseline using upper extremity motor impairments scales, Functional Independence Measure, aphasia and neglect scores. Number of movements and robotic assistance were compared between Session 2 (S2), 8 (8) and 16 (S16), Motricity Index between pre …and post-treatment. Correlation analyses explored predictors of motor performance. Results: Overall, number of movements and Motricity Index increased significantly while robot-assistance decreased. The mean number of movements per session correlated positively with baseline motor capacities but not with age, aphasia and neglect. However, the increase in Motricity index correlated negatively with baseline Motricity index and the increase in the number of movements correlated negatively with the number of movements at S2. Conclusion: High intensity robot-assisted training may be associated with motor improvement in subacute hemiparesis. More severely impaired patients may derive greater benefit from robot-assisted training; age, aphasia and neglect do not represent exclusion criteria. Show more

Keywords: Hemiparesis, upper limb, subacute stroke, robot-assisted training

DOI: 10.3233/RNN-140418

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 1, pp. 57-65, 2015

Authors: Araneda, Rodrigo | De Volder, Anne G. | Deggouj, Naïma | Philippot, Pierre | Heeren, Alexandre | Lacroix, Emilie | Decat, Monique | Rombaux, Philippe | Renier, Laurent

Article Type: Research Article

Abstract: Purpose: Tinnitus is the perception of a sound in the absence of external stimulus. Currently, the pathophysiology of tinnitus is not fully understood, but recent studies indicate that alterations in the brain involve non-auditory areas, including the prefrontal cortex. Here, we hypothesize that these brain alterations affect top-down cognitive control mechanisms that play a role in the regulation of sensations, emotions and attention resources. Methods: The efficiency of the executive control as well as simple reaction speed and processing speed were evaluated in tinnitus participants (TP) and matched control subjects (CS) in both the auditory and the visual modalities using …a spatial Stroop paradigm. Results: TP were slower and less accurate than CS during both the auditory and the visual spatial Stroop tasks, while simple reaction speed and stimulus processing speed were affected in TP in the auditory modality only. Conclusions: Tinnitus is associated both with modality-specific deficits along the auditory processing system and an impairment of cognitive control mechanisms that are involved both in vision and audition (i.e. that are supra-modal). We postulate that this deficit in the top-down cognitive control is a key-factor in the development and maintenance of tinnitus and may also explain some of the cognitive difficulties reported by tinnitus sufferers. Show more

Keywords: Tinnitus, attention, cognitive control, executive function, hearing impairment, prefrontal cortex, sensory processing, multisensory integration, spatial Stroop

DOI: 10.3233/RNN-140433

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 1, pp. 67-80, 2015

Authors: Terzi, Menderes Yusuf | Casalis, Pablo | Lang, Veronika | Zille, Marietta | Bründl, Elisabeth | Störr, Eva-Maria | Brawanski, Alexander | Vajkoczy, Peter | Thomale, Ulrich | Piña, Ana Luisa

Article Type: Research Article

Abstract: Purpose: Pigment epithelium-derived factor (PEDF) is a multifunctional protein with antiangiogenic, anti-inflammatory, neurotrophic and neurogenic properties. The effect of PEDF on traumatic brain injury (TBI) has not been explored. In this study, we aimed to show the in vivo effects of PEDF on lesion volume, cell death and cell proliferation after TBI. Methods: Rats were subjected to controlled cortical impact injury (CCII). PEDF mRNA brain levels were measured by RT-PCR. The lesion volume, cell proliferation, cell death and microglia activation were assessed in the brains of lesioned animals with intraventricular alzet infusion of PEDF or aCSF, and intraperitoneal injections of …BrdU. Results: We detected a significant increase of PEDF mRNA levels after TBI. PEDF intraventricular infusion showed no significant effect on the contusion volume, whereas the number of dead cells, activated microglia, BrdU-positive cells around the lesion were significantly decreased. In contrast, PEDF application increased cell proliferation in the ipsilateral subventricular zone. No effect was found on cell proliferation in the dentate gyrus. Conclusion: The present work indicates that PEDF acts as a multifunctional agent after TBI influencing cell death, inflammation and cell proliferation. Show more

Keywords: PEDF, traumatic brain injury, cell death, microglia, SVZ

DOI: 10.3233/RNN-140417

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 1, pp. 81-93, 2015