Restorative Neurology and Neuroscience - Volume 29, issue 3

Authors: Kang, Eun Kyoung | Kim, Yu Kyeong | Sohn, Hae Min | Cohen, Leonardo G. | Paik, Nam-Jong

Article Type: Research Article

Abstract: Purpose: Previous reports have suggested that noninvasive cortical stimulation could influence speech production in patients with chronic stroke. Here, we evaluated the hypothesis that cathodal transcranial DC stimulation (ctDCS), a technique that decreases excitability of stimulated cortical sites, applied over a healthy right Broca's homologue area could improve picture naming in patients with post-stroke aphasia. Methods: Ten right-handed patients with post-stroke aphasia were enrolled in this double blind, counterbalanced sham-controlled, crossover study. Each patient received an intervention of ctDCS (2 mA for 20 min) and of sham tDCS (2 mA for 1 min) daily for 5 consecutive days in a …randomized crossover manner with a minimum interval of one week between interventions, over a healthy right Broca's homologue area using a left supraorbital anode and simultaneous daily sessions of conventional word-retrieval training. The primary endpoint measure of this study was a standardized, validated Korean version of the Boston Naming Test, which is a measure of picture naming skills. Results: ctDCS was not found to have any adverse effects. Furthermore, significantly improved picture naming (p = 0.02) was observed at 1 hour following the last (5th) ctDCS treatment session, but no changes were observed after sham tDCS. Conclusion: These results demonstrate that cathodal tDCS over the right healthy Broca's homologue area with a left supraorbital anodal location can improve picture naming task performance in post-stroke aphasia. Show more

Keywords: Aphasia, stroke, cortical stimulation, transcranial direct current stimulation

DOI: 10.3233/RNN-2011-0587

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 3, pp. 141-152, 2011

Authors: Jarosik, J. | Legutko, B. | Werner, S. | Unsicker, K. | von Bohlen und Halbach, O.

Article Type: Research Article

Abstract: Purpose: Several members of the fibroblast growth factor (FGF) family have been shown to be dysregulated in individuals with major depression, and treatment with antidepressants has been reported to increase FGF-2 mRNA levels in the forebrain. Methods: We have used the tail suspension test (TST), and olfactory bulbectomy (OBX), and FGF-2 deficient mice to investigate putative roles of FGF-2 as an antidepressant and mediator of antidepressive drug actions. Results: FGF-2 applied intraventricularly generated antidepressant-like effects in the TST. FGF-2, similar to the antidepressant amitriptyline, attenuated neuron demise in the piriform cortex and posterolateral cortical nucleus of the amygdala following OBX. …Moreover, OBX induced reduction in hippocampal neurogenesis could be ameliorated by subsequent treatment with either amitriptyline or FGF-2. Furthermore, FGF-2 was effective in reversing depressive-like behavior induced by OBX, monitored in the locomotor activity and the passive avoidance test. In bulbectomized FGF-2 deficient mice, treatment with amitriptyline protected neurons, but failed to reverse behavioral alterations. Conclusions: Together, these results suggest that FGF-2 constitutes both a potential target for antidepressive treatments and an important growth factor in the cytokine network underlying the actions of antidepressive drugs. The results further suggest a requirement of endogenous FGF-2 for mediating behavioral, but not neuroprotective actions of amitriptyline. Show more

Keywords: Mice, fibroblast growth factor, FGF-2 knockout, behavior, dendritic spines, neurogenesis, depression

DOI: 10.3233/RNN-2011-0588

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 3, pp. 153-165, 2011

Authors: Chaieb, Leila | Antal, Andrea | Paulus, Walter

Article Type: Research Article

Abstract: Purpose: External transcranial electric and magnetic stimulation techniques allow for the fast induction of sustained and measurable changes in cortical excitability. Here we aim to develop a paradigm using transcranial alternating current (tACS) in a frequency range higher than 1 kHz, which potentially interferes with membrane excitation, to shape neuroplastic processes in the human primary motor cortex (M1). Methods: Transcranial alternating current stimulation was applied at 1, 2 and 5 kHz over the left primary motor cortex with a reference electrode over the contralateral orbit in 11 healthy volunteers for a duration of 10 min at an intensity of 1 …mA. Monophasic single- pulse transcranial magnetic stimulation (TMS) was used to measure changes in corticospinal excitability, both during and after tACS in the low kHz range, in the right hand muscle. As a control inactive sham stimulation was performed. Results: All frequencies of tACS increased the amplitudes of motor- evoked potentials (MEPs) up to 30–60 min post stimulation, compared to the baseline. Two and 5 kHz stimulations were more efficacious in inducing sustained changes in cortical excitability than 1 kHz stimulation, compared to sham stimulation. Conclusions: Since tACS in the low kHz range appears too fast to interfere with network oscillations, this technique opens a new possibility to directly interfere with cortical excitability, probably via neuronal membrane activation. It may also potentially replace more conventional repetitive transcranial magnetic stimulation (rTMS) techniques for some applications in a clinical setting. Show more

Keywords: Primary motor cortex (M1), transcranial magnetic stimulation (TMS), neuroplasticity, transcranial alternating stimulation (tACS), high frequency stimulation (HFS)

DOI: 10.3233/RNN-2011-0589

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 3, pp. 167-175, 2011

Authors: Meng, Li | Ouyang, Jian | Zhang, Haitao | Wen, Yanting | Chen, Junhao | Zhou, Jinyong

Article Type: Research Article

Abstract: Purpose: Hematopoietic stem cell transplantation (HSCT) has been proposed as a novel therapy for multiple sclerosis (MS). CD4 + CD25 + regulatory T cells (Tregs) expressing Foxp3 play an important role in the maintenance of immune tolerance to self. Our study was conducted to confirm the efficiency of nonmyeloablative conditioning and syngeneic bone marrow transplantation (BMT) on experimental autoimmune encephalomyelitis (EAE) mice and to determine whether Tregs plays a role in the underlying mechanism. Methods: EAE were induced in C57BL/6 mice and were randomly divided into 4 groups: the Conditioning group received the conditioning regimen, the Normal-EAE BMT group received …conditioning and bone marrow (BM) grafts from normal mice, the EAE-EAE BMT group received conditioning and BM grafts from EAE mice and the EAE control group received no further therapy. The cumulative clinical score was used to assess the efficacy of the different treatments, and the proportion of Tregs in the spleen was measured by flow cytometry on day 40, 80 and 120 after BMT. Foxp3 mRNA expression was assessed by real-time PCR, and the expression of Foxp3 protein was tested by western blot on day 120 after BMT. Results: Conditioning and conditioning with BMT led to a significant clinical improvement on day 80 after BMT compared with EAE without further treatment. On day 120 after BMT, the clinical score of the Conditioning group showed no significant difference from that of the EAE control group, whereas BMT led to a further amelioration of the disease score. On day 80 and day 120 after BMT, the proportions of Tregs of the two BMT groups were significantly higher than that in EAE control group, whereas no statistically significant difference was found between the Conditioning group and the EAE control group. On day 120 after BMT, the Foxp3 mRNA level and Foxp3 protein expression was higher in the two BMT groups than in EAE control group or Conditioning group. Conclusions: Nonmyeloablative conditioning could temporarily reverse already established EAE, but it was not sufficient for the induction of long-term EAE remission. Transplantation by BM cells from healthy or diseased donors was necessary and responsible for complete and long-time remission of EAE, and these beneficial effects may be the result of the induction of Tregs and the Treg-related factor Foxp3. Show more

Keywords: Syngeneic bone marrow transplantation, multiple sclerosis, experimental autoimmune encephalomyelitis, CD4 + CD25 + Foxp3 + regulatory T cells

DOI: 10.3233/RNN-2011-0590

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 3, pp. 177-185, 2011

Authors: Tewarie, R.D.S. Nandoe | Bossers, K. | Ritfeld, G.J. | Blits, B. | Grotenhuis, J.A. | Verhaagen, J. | Oudega, M.

Article Type: Research Article

Abstract: Purpose: The assessment of the capacity of bone marrow stromal cells (BMSC) to repair the nervous system using gene expression profiling. The evaluation of effects of long-term culturing on the gene expression profile of BMSC. Methods: Fourty four k whole genome rat microarrays were used to study gene expression of cultured BMSC at passage (P)3 and to compare expression profiles between P3 and P14 BMSC. Quantitative PCR was employed to validate the microarray results. Results: P3 BMSC expressed genes involved in neural developmental events such as glial differentiation, neuron proliferation, and neurite formation. They also express genes encoding for growth …factors and for proteins involved in growth factor signaling. A total of 6687 genes were co-expressed in P3 and P14 BMSC. Of these co-expressed genes, 3% (202 genes) was differentially expressed with 159 genes higher in P3 BMSC and 43 genes higher in P14 BMSC. The gene expression patterns were independently validated using quantitative PCR. Functional data mining by Gene Ontology (GO)-analysis revealed that 85/159 and 22/43 genes were annotated in the GO database. In P3 BMSC, 53 GO-classes were overrepresented with several involved in organ development, cell proliferation, and neural repair. In P14 BMSC, three GO-classes were overrepresented with one involved in organ development. Conclusions: Our gene profiling results suggested a decreased plasticity and repair aptitude of long-term cultured BMSC. Our data indicated the use of early passage BMSC for neural repair approaches. Show more

Keywords: BMSC, cell culture, stem cells, gene profiling, microarray

DOI: 10.3233/RNN-2011-0591

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 3, pp. 187-201, 2011

Authors: Klingner, Carsten M. | Volk, Gerd F. | Maertin, Antje | Brodoehl, Stefan | Burmeister, Hartmut P. | Guntinas-Lichius, Orlando | Witte, Otto W.

Article Type: Research Article

Abstract: Purpose: Bell's palsy, a unilateral, idiopathic facial nerve palsy, is a common disorder that is generally followed by a good recovery of function. The aim of this study was to investigate the impact of such a transiently decreased motor control (without deafferentation) on the functional reorganization of the brain. Methods: To address this issue, functional MRI was applied to 10 patients in the acute state of Bell's palsy and after their complete clinical recovery. The functional paradigm consisted of unilateral facial movements with the affected as well as the non-affected side. Results: We found an overactivity of several brain areas …contralateral to the palsy that are related to error detection and sensory-motor integration in the acute stage and motor integration and control in the follow-up. Functional connectivity was disrupted in the affected cortical motor system during the acute stage of Bell's palsy compared to the follow-up. This altered connectivity was found mostly between motor areas in the hemisphere contralateral to the paretic side, whereas the interhemispherical connectivity remained largely stable. Conclusion: Our results indicate that a transient peripheral deefferentation causes functional reorganization in the brain that partly persists even after an apparently complete clinical recovery. Show more

Keywords: Facial nerve, palsy, fMRI, BOLD, connectivity

DOI: 10.3233/RNN-2011-0592

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 3, pp. 203-214, 2011