Restorative Neurology and Neuroscience - Volume 32, issue 4

Authors: Schlachetzki, Johannes C.M. | Marxreiter, Franz | Regensburger, Martin | Kulinich, Anna | Winner, Beate | Winkler, Jürgen

Article Type: Research Article

Abstract: Purpose: Parkinson's disease (PD) is characterized by striatal synaptic deafferentation followed by dopaminergic cell death in the substantia nigra pars compacta. Not only degenerative, but also regenerative, compensatory changes at distant sites of the primary lesion may occur in PD. The aim of the study was to analyze the temporal pattern of axonal and glial responses over a time course of six weeks post-lesioning. Methods: For this aim, 6-hydroxydopamine (6-OHDA) was injected unilaterally into the medial forebrain bundle and both lesioned and non-lesioned striata were analyzed. Results: We detected increased tyrosine hydroxylase (TH) immunoreactivity within the non-lesioned striatum six weeks …after injection indicative either of increased TH expression or compensatory neuritic changes. An increased number of microglial cells was present in both lesioned and unlesioned striata. There was no obvious change in microglial phenotype or in pro-inflammatory cytokine gene expression within the striatum without any apparent switch into a pro-inflammatory phenotype. No changes were observed in the number of mature oligodendrocytes. Conclusions: This temporal pattern shows, that the non-lesioned striatum undergoes profound changes, involving increased TH expression accompanied by a glial response. A better understanding of this complex interplay of neuronal as well as glial components not only within the lesioned, but also non-lesioned striatum may help to restore local neural circuits in PD. Show more

Keywords: Parkinson's disease, 6-hydroxydopamine, axonal degeneration, microglia, astrocyte, oligodendrocyte

DOI: 10.3233/RNN-130371

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 4, pp. 447-462, 2014

Authors: Claros-Salinas, Dolores | Greitemann, Georg | Hassa, Thomas | Nedelko, Violetta | Steppacher, Inga | Harris, Joseph Allen | Schoenfeld, Mircea Ariel

Article Type: Research Article

Abstract: Purpose: The loss of calculation skills due to brain lesions leads to a major reduction in the quality of life and is often associated with difficulties of returning to work and a normal life. Very little is known about the neural mechanisms underlying performance improvement due to calculation training during rehabilitation. The current study investigates the neural basis of training-induced changes in patients with acalculia following ischemic stroke or traumatic brain lesions. Methods: Functional hemodynamic responses (fMRI) were recorded in seven patients during calculation and perceptual tasks both before and after acalculia training. Results: Despite the heterogeneity of brain lesions …associated with acalculia in our patient sample, a common pattern of training-induced changes emerged. Performance improvements were associated with widespread deactivations in the prefrontal cortex. These deactivations were calculation-specific and only observed in patients exhibiting a considerable improvement after training. Conclusion: These findings suggest that the training-induced changes in our patients rely on an increase of frontal processing efficiency. Show more

Keywords: Acalculia, training-induced activity changes, fMRI, calculation training

DOI: 10.3233/RNN-130342

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 4, pp. 463-472, 2014

Authors: Suzuki, Yoshihisa | Ishikawa, Namiko | Omae, Kaoru | Hirai, Tatsuya | Ohnishi, Katsunori | Nakano, Norihiko | Nishida, Hidetaka | Nakatani, Toshio | Fukushima, Masanori | Ide, Chizuka

Article Type: Research Article

Abstract: Purpose: This study was conducted to assess the safety and feasibility of intrathecal transplantation of autologous bone marrow-derived mononuclear cells for the treatment of patients with spinal cord injury. Methods: Ten patients were included in the study. Approximately 120 ml of bone marrow aspirate was obtained from bilateral iliac bone of patients with spinal cord injury. Isolation of mononuclear cells was performed using Ficoll density-gradient centrifugation. Bone marrow mononuclear cells were transplanted into cerebrospinal fluid by lumbar puncture. Functional tests were performed prior to the cell transplantation and six months after cell transplantation. The patients were carefully observed for up …to six months. Results: In 5 patients with AIS A prior to cell transplantation, 1 patient converted to AIS B six months after cell transplantation. In 5 patients with AIS B, 1 patient converted to AIS D and 2 patients to AIS C. MRI did not show any complication. Two patients showed slight anemia after aspiration of bone-marrow cells, which returned to normal level within a several weeks. Conclusion: The results of this study suggest that this method may be safe and feasible. Show more

Keywords: Central nervous system regeneration, spinal cord injury treatment, bone marrow mononuclear cell, clinical study, cell transplantation

DOI: 10.3233/RNN-130363

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 4, pp. 473-482, 2014

Authors: Martin, Paula I. | Treglia, Ethan | Naeser, Margaret A. | Ho, Michael D. | Baker, Errol H. | Martin, Elizabeth G. | Bashir, Shahid | Pascual-Leone, Alvaro

Article Type: Research Article

Abstract: Purpose: The purpose of this study was to investigate: 1) the feasibilty of administering a modified CILT (mCILT) treatment session immediately after TMS; and 2) if this combined therapy could improve naming and elicited propositional speech in chronic, nonfluent aphasia. Methods: Two chronic stroke patients with nonfluent aphasia (mild-moderate and severe) each received twenty minutes of rTMS to suppress the right pars triangularis, followed immediately by three hours of mCILT (5 days/week, 2 weeks). (Each patient had received TMS alone, 2–6 years prior.) Language evaluations were performed pre- TMS+mCILT, and post- at 1-2 months, and 6 or 16 months. Results: …Both patients showed significant improvements in naming pictures, and elicited propositional speech at 1-2 months post- TMS+mCILT. The improved naming was still present at 6 months post- TMS+mCILT for P2; but not at 16 months post- TMS+mCILT for P1. Conclusions: It is feasible to administer mCILT for three hours immediately after a TMS session. It is unknown if the significant improvements in naming pictures, and elicited propositional speech were associated with the second series of TMS, or this first series of mCILT, or a combination of both. A larger, sham controlled clinical trial is warranted. Show more

Keywords: TMS, speech therapy, constraint-induced language therapy, aphasia, stroke rehabilitation

DOI: 10.3233/RNN-130365

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 4, pp. 483-505, 2014

Authors: Oelschläger, M. | Pfannmöller, J. | Langner, I. | Lotze, M.

Article Type: Research Article

Abstract: Purpose: The primary somatosensory cortex (S1) is somatotopically reorganized after limb amputation. The duration of the amputation, the intensity of phantom limb pain but also a multifactoral model of altered cerebral input have been discussed to be associated with cortical changes. Patients with finger amputation rarely show phantom limb pain, the deafferented cortical area is small but other fingers might well overtake function. Method: We selected a group of index finger amputated patients and performed a high resolution (in plane: 1.5 mm2 ) S1-mapping during tactile stimulation of finger tips. Result: We found an interhemispheric imbalance of the distance between …the thumb and middle finger only for the patient-group. When patients used their middle finger more they showed less interhemispheric imbalance, increased spatial tactile discrimination and increased fMRI-activation in response to stimulation. Phantom limb pain was not associated with somatotopic representation parameters in S1. Conclusions: Overall, our fMRI-data point to a usage dependent plasticity of Brodmann's area 3b in man. Show more

Keywords: Amputation, cortical plasticity, usage factor, somatotopy, primary somatosensory cortex, S1, reorganization, fMRI

DOI: 10.3233/RNN-130380

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 4, pp. 507-515, 2014

Authors: Gharabaghi, Alireza | Naros, Georgios | Walter, Armin | Grimm, Florian | Schuermeyer, Marc | Roth, Alexander | Bogdan, Martin | Rosenstiel, Wolfgang | Birbaumer, Niels

Article Type: Research Article

Abstract: Purpose: Today's implanted brain-computer interfaces make direct contact with the brain or even penetrate the tissue, bearing additional risks with regard to safety and stability. What is more, these approaches aim to control prosthetic devices as assistive tools and do not yet strive to become rehabilitative tools for restoring lost motor function. Methods: We introduced a less invasive, implantable interface by applying epidural electrocorticography in a chronic stroke survivor with a persistent motor deficit. He was trained to modulate his natural motor-related oscillatory brain activity by receiving online feedback. Results: Epidural recordings of field potentials in the beta-frequency band projecting …onto the anatomical hand knob proved most successful in discriminating between the attempt to move the paralyzed hand and to rest. These spectral features allowed for fast and reliable control of the feedback device in an online closed-loop paradigm. Only seven training sessions were required to significantly improve maximum wrist extension. Conclusions: For patients suffering from severe motor deficits, epidural implants may decode and train the brain activity generated during attempts to move with high spatial resolution, thus facilitating specific and high-intensity practice even in the absence of motor control. This would thus transform them from pure assistive devices to restorative tools in the context of reinforcement learning and neurorehabilitation. Show more

Keywords: Electrocorticography, neuroprosthetics, epidural implant, brain-computer interface, brain-machine interface, neurorehabilitation, stroke

DOI: 10.3233/RNN-140387

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 4, pp. 517-525, 2014

Authors: Tahtis, Vassilios | Kaski, Diego | Seemungal, Barry M.

Article Type: Research Article

Abstract: Purpose: Non-invasive brain stimulation with transcranial direct current stimulation (tDCS) modulates cortical excitability and improves upper limb motor performance when applied to chronic stroke patients. The objective was to evaluate whether tDCS can influence gait function in sub-acute stroke patients. Methods: We assessed the effect of single session, bi-cephalic tDCS on gait performance in 14 subacute patients with stroke involving the cerebral hemisphere (2–8 weeks post-stroke) in a double-blinded, sham-controlled study. Patients were randomly allocated to receive either active (n = 7) or sham (n = 7) tDCS. The anodal electrode was placed on the scalp over the ipsilesional lower …limb primary motor cortex and the cathode was placed over the contralesional leg motor cortex. Gait performance was measured using the Timed Up and Go test and the Performance Oriented Mobility Assessment before and after active or sham tDCS. Results: The tDCS group was significantly quicker in the Timed Up and Go test in the tDCS group, compared to the sham group (p = 0.018). The Performance Oriented Mobility Assessment was not different between groups (p = 0.897). Conclusions: This is the first study to examine the effects of tDCS on gait in stroke patients in the sub-acute stage. Active tDCS improved gait performance (Timed Up and Go) in stroke patients, despite no changes to limb biomechanics of the hemiparetic side (Performance Oriented Mobility Assessment), as compared to sham stimulation. These results suggest that tDCS could be used as a therapeutic adjunct for gait rehabilitation following stroke. Show more

Keywords: Stroke, gait, transcranial direct current stimulation, rehabilitation, subacute

DOI: 10.3233/RNN-140393

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 4, pp. 527-532, 2014

Authors: Chen, Li | Wang, Xiaoting | Chen, Xinran | Xing, Shihui | Zhang, Jian | Li, Jingjing | Dang, Chao | Liu, Gang | Dang, Ge | Zeng, Jinsheng

Article Type: Research Article

Abstract: Purpose: Tongxinluo, a well-known traditional Chinese medicine complex, has been widely used for the treatment of cerebrovascular diseases in China. The present study was to explore whether treatment with tongxinluo could improve neurological function and alleviate secondary damage in the ipsilateral thalamus after focal cortical infarction in hypertensive rats. Methods: Tongxinluo was given through oral gavage starting 24 h after distal middle cerebral artery occlusion (MCAO). Neurological function was assessed and then rats were sacrificed 7 and 14 days after MCAO. Brains were harvested for examining infarction volume, Nissl staining and immunofluorescence analysis. Results: Compared with vehicle treatment, tongxinluo remarkably …improved neurological function without reducing infarction volume, attenuated neuronal loss and astrocyte activation in the ipsilateral thalamus 7 and 14 days after MCAO (all p < 0.05). Also, tongxinluo markedly increased the number of BrdU+/nestin+ and BrdU+/NeuN+ cells 14 days after MCAO. Moreover, vascular density, the number of BrdU+ vascular endothelial cells, and vascular perimeter in the ipsilateral thalamus were markedly increased in the tongxinluo group relative to that of the vehicle group (all p < 0.05). Conclusion: Administration of tongxinluo 24 h after cortical infarction may promote neurogenesis and angiogenesis in the ipsilateral thalamus and improves neurological function after cortical infarction in rats. Show more

Keywords: Tongxinluo, neurogenesis, angiogenesis, focal cerebral infarction

DOI: 10.3233/RNN-140403

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 4, pp. 533-546, 2014

Authors: Tatarishvili, Jemal | Oki, Koichi | Monni, Emanuela | Koch, Philipp | Memanishvili, Tamar | Buga, Ana-Maria | Verma, Vivek | Popa-Wagner, Aurel | Brüstle, Oliver | Lindvall, Olle | Kokaia, Zaal

Article Type: Research Article

Abstract: Purpose: Induced pluripotent stem cells (iPSCs) improve behavior and form neurons after implantation into the stroke-injured adult rodent brain. How the aged brain responds to grafted iPSCs is unknown. We determined survival and differentiation of grafted human fibroblast-derived iPSCs and their ability to improve recovery in aged rats after stroke. Methods: Twenty-four months old rats were subjected to 30 min distal middle cerebral artery occlusion causing neocortical damage. After 48 h, animals were transplanted intracortically with human iPSC-derived long-term neuroepithelial-like stem (hiPSC-lt-NES) cells. Controls were subjected to stroke and were vehicle-injected. Results: Cell-grafted animals performed better than vehicle-injected recipients in …cylinder test at 4 and 7 weeks. At 8 weeks, cell proliferation was low (0.7 %) and number of hiPSC-lt-NES cells corresponded to 49.2% of that of implanted cells. Transplanted cells expressed markers of neuroblasts and mature and GABAergic neurons. Cell-grafted rats exhibited less activated microglia/macrophages in injured cortex and neuronal loss was mitigated. Conclusions: Our study provides the first evidence that grafted human iPSCs survive, differentiate to neurons and ameliorate functional deficits in stroke-injured aged brain. Show more

Keywords: Stroke, neuroregeneration, inflammation, reprogramming, recovery, neural stem cell, aging, transplantation

DOI: 10.3233/RNN-140404

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 4, pp. 547-558, 2014