Restorative Neurology and Neuroscience - Volume 28, issue 6

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

Article Type: Research Article

Abstract: The journal Restorative Neurology and Neuroscience (RNN) is focused on the emerging field of brain plasticity, repair and rehabilitation, including original and review papers both in basic research (in vitro studies, animal experiments) and in the clinical domain, including brain imaging studies. The publication of special issues on vital topics, summarizing the work of leading experts in the field of restoration and plasticity has become a major strategy of RNN and has attracted worldwide attention. Special …issues are typically organized by specialized guest-editors familiar with the respective science field. Special issues cover a particular sub-discipline and often contain laboratory review papers. The first special issue appeared in 1990, and until today RNN has published a total of 25 special issues on a variety of basic science and clinical matters. In this way, RNN promotes the dissemination of information in the field of neuroplasticity, repair and rehabilitation, providing the reader with up-to-date information prepared by leading experts in the field. Show more

DOI: 10.3233/RNN-2010-0581

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 6, pp. 719-728, 2010

Authors: Liepert, Joachim | Binder, Christian

Article Type: Research Article

Abstract: Background: Spasticity manifesting as a dysbalance between extensor and flexor muscles may contribute to an impaired hand function. We studied clinical (n=10 patients) and electrophysiological (n=9 patients) changes produced by vibration of forearm extensor muscles (FEM) in chronic stroke patients with spastic hemiparesis. Methods: In Exp. 1, the Box and Block Test (BBT) was applied to test dexterity before and after 5 minutes of FEM vibration. In Exp. 2, transcranial magnetic stimulation was used …to study the cortical silent period (CSP) before and during FEM vibration. Recordings were taken from the antagonistic flexor carpi radialis muscle. Results: After vibration, performance of the BBT was improved by 20%. The effect persisted for at least 10–15 minutes. Vibration induced a prolongation of the CSP. This effect occurred in the affected and non-affected side to a similar degree. The magnitude of performance changes and CSP changes was not correlated. Conclusions: FEM vibration enhances inhibitory neuronal circuits targeting the antagonistic forearm flexor muscles and is associated with an improved dexterity in the spastic arm. It might become a supporting tool in the motor recovery of spastic hemiparesis. Show more

Keywords: Spastic hemiparesis, stroke, vibration, dexterity, cortical silent period, transcranial magnetic stimulation

DOI: 10.3233/RNN-2010-0541

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 6, pp. 729-735, 2010

Authors: Nedelko, Violetta | Hassa, Thomas | Hamzei, Farsin | Weiller, Cornelius | Binkofski, Ferdinand | Schoenfeld, Mircea Ariel | Tüscher, Oliver | Dettmers, Christian

Article Type: Research Article

Abstract: Purpose: Recent studies have found age-related BOLD signal changes in several areas of the human brain. We investigated whether such changes also occur in brain areas involved in the processing of motor action observation and imagery. Methods: Functional magnetic resonance imaging with an experimental paradigm in which motor acts had to be observed and/or imagined from a first person perspective was performed in twenty-six subjects. Results: In line with previous work action observation and imagery induced …BOLD signal increases in similar areas, predominantly in the premotor and parietal cortex. In contrast to young subjects the elderly displayed a stronger activity in most activated brain areas indicative of compensatory activity for the age-related decline of neural structures. Importantly, activity in the ventrolateral premotor cortex and inferior parietal cortex, seminal areas of the mirror neuron system, did not exhibit activity changes as a function of age. Conclusion: These findings suggest that activity within the mirror neuron system is not age dependent and provide a neural basis for therapeutical interventions and novel rehabilitation treatments such as video therapy. Show more

Keywords: fMRI, mirror neuron system, age-dependent changes, action imagery, action observation, object related actions

DOI: 10.3233/RNN-2010-0542

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 6, pp. 737-747, 2010

Authors: Rougier, P. | Boudrahem, S.

Article Type: Research Article

Abstract: Purpose: To assess whether insights from postural control without additional visual feedback (VFB) could be gained to explain the possible VFB effects (or non-effects) on upright stance performance. Methods: The center-of-pressure (CP) displacements of 39 patients with a recent hemispheric stroke (93 days ± 56; mean ± s.d.) were analyzed in two conditions (eyes open and VFB) through various classical parameters and fractional Brownian motion (fBm) modeling. Correlations between their ability to use the …VFB technique appropriately and parameters assessing the eyes open condition were also computed. Results: The fBm modeling showed that the VFB technique improves the control of the CP trajectories over the longer time intervals. In both conditions, the patients with right hemiparesis, compared to those with left hemiparesis, demonstrated improved control of their CP displacement along the AP axis over the shortest time intervals. Overall, 28% of the patients did not use the VFB technique. The correlation analysis indicated that the larger the spontaneous CP movements in the eyes open condition, the greater the effect of the VFB technique. Conclusions: By emphasizing its particular effects and the profile of the patients who used the technique, these data specify the conditions allowing hemiparetic patients to use the VFB technique appropriately and immediately. Show more

Keywords: Postural control-visual feedback-hemiparesis-center of pressure-rehabilitation

DOI: 10.3233/RNN-2010-0544

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 6, pp. 749-759, 2010

Authors: Alexanian, Arshak R. | Kwok, Wai-Meng | Pravdic, Danijel | Maiman, Dennis J. | Fehlings, Michael G.

Article Type: Research Article

Abstract: Purpose: We recently developed a new method for efficient generation of neural-like cells from mice bone marrow (BM)-derived mesenchymal stem cells (MSC) by exposing MSCs to epigenetic modifiers and a neural stem cell environment. These neurally induced MSCs (NI-MSCs) differentiate into neuronal- and glial-like cells in vitro, release neurotrophic factors NGF and BDNF, survive and integrate after transplantation in intact spinal cord. The aim of this study was to determine whether transplanted NI-MSCs survive, …differentiate, and integrate in injured spinal cord (ISC) rats and promote functional recovery. Methods: Twenty rats, half grafted with MSCs and half with NI-MSCs, were used for survival and differentiation studies. Results were analyzed using triple-labeled immunohistochemistry. For motor function studies the 3 group of adult female Sprague Dawley rats received PBS (vehicle), MSCs, or NI-MSCs, respectively. Functional outcome was measured using the BBB scale. Results: Results demonstrated gradual improvement of locomotor function in NI-MSC-transplanted rats in comparison to vehicle and non-modified MSC-transplanted animals, with statistically significant differences at 7, 14, and 21 days post transplantation. Immunocytochemical studies revealed poor survival of NI-MSCs within the ISC as early as 3 weeks after transplantation. Conclusions: Thus, there is a correlation between the degree of surviving NI-MSCs and extent of functional recovery. Show more

Keywords: Mesenchymal stem cells, neural cells, epigenetic, spinal cord, transplantation, survival, differentiation, regeneration

DOI: 10.3233/RNN-2010-0547

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 6, pp. 761-767, 2010

Authors: DeFina, Philip A. | Fellus, Jonathan | Thompson, James W.G. | Eller, Monika | Moser, Rosemarie Scolaro | Frisina, Pasquale G. | Schatz, Philip | DeLuca, John | Zigarelli-McNish, Maria | Prestigiacomo, Charles J.

Article Type: Research Article

Abstract: Purpose: To evaluate the efficacy of an Advanced Care Protocol (ACP) in improving rates of clinical progression and emergence in patients with Severe Disorders of Consciousness (SDOC). Methods: Forty-one patients with SDOC were assigned to groups: Vegetative State (VS) traumatic etiology (VS-TBI), VS non-traumatic etiology (VS-NTBI), Minimally Conscious State (MCS-TBI), MCS non-traumatic etiology (MCS-NTBI). Design was a within-subjects retrospective case series measuring pre-post ACP intervention data. The ACP was administered …sequentially over 12 weeks, incorporating traditional therapies (occupational, physical, speech), pharmaceuticals, median nerve stimulation, and neutraceuticals. Main Outcome Measures were: Pre- and post-treatment Disability Rating Scale (DRS), Functional Independence Measure (FIM), Glasgow Coma Scale (GCS), and Coma Recovery Scale-Revised (CRS-R); clinical diagnosis (VS, MCS, emerged) using criteria from the American Academy of Neurology and Mohonk Report. Results: Patients significantly improved across all outcome measures, from baseline to discharge. Clinical improvement of 100% of MCS patients and 78–86% of VS patients was observed following ACP treatment. Significant differences between ACP vs. the published "standard of care" rates, in favor of the ACP, based on DRS scores and on clinical status at discharge. Conclusions: These strikingly positive results of a novel multimodal intervention are a valuable contribution to this frontier of investigation. Show more

DOI: 10.3233/RNN-2010-0548

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 6, pp. 769-780, 2010

Authors: García-Alías, Guillermo | Torres-Espín, Abel | Vallejo, Carolina | Navarro, Xavier

Article Type: Research Article

Abstract: Purpose: To evaluate the effects on locomotion and lumbar motoneuron function after a contusion to the midthoracic spinal cord of the rat. Methods: Five animals received a moderate contusion on T8, and over 28 days postoperation (dpo) locomotion and motor electrophysiological outcome were compared with five sham-operated animals. Results: At 28 dpo, the contused animals supported their body weight (BBB score =11.5 ± 0.5) and stepped uncoordinatedly. Motor evoked potentials recorded in the tibialis anterior (TA) …and plantar muscles (PL), and longitudinal interlimb reflexes recorded in the TA muscles were abolished. The M wave recorded in the TA showed a decrease in amplitude by 7 dpo, which remained invariable until the end of the evaluation (88 ± 3% of {preoperative} values), whereas in the PL muscle it was not affected. Injured animals presented hyperreflexia, as shown by an increased H/M ratio. Histological analysis showed similar number of retrogradely traced TA motoneurons between groups, and that contused animals presented hypertrophied astrocytes in the most rostral but not caudal segments of the lumbar enlargement. Conclusion: These results indicate that after contusion to the thoracic spinal cord, the lumbar segments undergo structural and functional changes, following a rostro-caudal gradient extension. Show more

Keywords: Motoneuron, motor evoked potentials, nerve conduction, lumbar, spinal cord injury, reactive astrocytes

DOI: 10.3233/RNN-2010-0549

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 6, pp. 781-792, 2010

Authors: Hess, R. F. | Mansouri, B. | Thompson, B.

Article Type: Research Article

Abstract: Purpose: The present treatments for amblyopia are predominately monocular aiming to improve the vision in the amblyopic eye through either patching of the fellow fixing eye or visual training of the amblyopic eye. This approach is problematic, not least of which because it rarely results in establishment of binocular function. Recently it has shown that amblyopes possess binocular cortical mechanisms for both threshold and suprathreshold stimuli. Methods: We outline a novel procedure for measuring …the extent to which the fixing eye suppresses the fellow amblyopic eye, rendering what is a structurally binocular system, functionally monocular. Results: Here we show that prolonged periods of viewing (under the artificial conditions of stimuli of different contrast in each eye) during which information from the two eyes is combined leads to a strengthening of binocular vision in strabismic amblyopes and eventual combination of binocular information under natural viewing conditions (stimuli of the same contrast in each eye). Concomitant improvement in monocular acuity of the amblyopic eye occurs with this reduction in suppression and strengthening of binocular fusion. Furthermore, in a majority of patients tested, stereoscopic function is established. Conclusions: This provides the basis for a new treatment of amblyopia, one that is purely binocular and aimed at reducing suppression as a first step. Show more

Keywords: Amblyopia, global motion, contrast, binocular summation, dichoptic interaction, treatment of amblyopia

DOI: 10.3233/RNN-2010-0550

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 6, pp. 793-802, 2010

Authors: Finberg, John P.M. | Gluzman, Zoya | Reshef, Michal | Loboda, Yelena | Mohsen, Usama | Bressler-Stramer, Tal | Miari, Reem | Gepstein, Lior | Marom, Shimon | Feld, Yair

Article Type: Research Article

Abstract: Purpose: A number of neurological disorders are marked by increased or aberrant frequency of neuronal discharge in specific parts of the brain. Administration of drugs such as antiepileptic compounds results in the depression of neuronal activity in the whole brain, with the potential for serious side-effects. In the search for additional therapies to reduce the unphysiological electrical activity of over-active brain foci, we have examined the effect of fibroblasts transplanted to areas responsible for motor …dysfunction in hemi-parkinsonian rats, since bursting synchronous discharges in internal segment of globus pallidus (GPi) are thought to be partially responsible for the movement disorders of PD. Fibroblasts express gap junctions and ion channels, and so, when transplanted to brain tissue, can potentially modulate excessive electrical activity. Methods: Neonatal cortical neurons were cultured on multi-electrode arrays, and their electrical activity was evaluated before and after fibroblast seeding. Unilateral 6-hydroxydopamine (6-OHDA) lesion was carried out in Fischer rats. Lesioned or control rats were transplanted with either syngeneic dermal fibroblasts, microfine glass beads, ibotenic acid, or physiological saline, in the entopeduncular nucleus (EP). Apomorphine-induced rotational behavior and L-dopa-induced dyskinetic movements were evaluated before transplantation (baseline) and 2, 4, 8, 12, and 24 weeks following transplantation. Following behavioral experiments, rats were perfused with 4% formaldehyde in PBS for immunohistochemical study of the brain. Results: We demonstrate in vitro that the introduction of fibroblasts into a network of neurons does not interfere with overall functional measures of activity, while moderately altering the characteristics of synchronous neuronal discharge. In rats with unilateral 6-hydroxydopamine lesions of the nigro-striatal dopaminergic pathway, apomorphine-induced rotations were reduced by more than 60% following ipsilateral transplantation of fibroblasts to the EP. L-Dopa-induced dyskinesia was also significantly reduced. Transplantation of inert microspheres, or chemical lesion of the same area with ibotenic acid, did not produce beneficial effects on parkinsonian symptomatology. Conclusion: Fibroblast transplantation could be an alternative treatment strategy for the parkinsonian patient. Show more

Keywords: 6-hydroxydopamine, entopeduncular nucleus, L-dopa-induced dyskinesia, apomorphine-induced rotation, multi-electrode array, cell transplantation

DOI: 10.3233/RNN-2010-0551

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 6, pp. 803-815, 2010

Authors: Türkyılmaz, Canan | Türkyılmaz, Zafer | Önal, Esra | Atalay, Yıldız | Söylemezoğlu, Figen | Celasun, Bülent

Article Type: Research Article

Abstract: Purpose: The pre and post-treatment effects of L-carnitine on apoptotic cell death due to hypoxia-ischemia in various regions of the brains of seven-day-old rats were investigated. Methods: L-carnitine (group 1; n=8) or saline (group 2; n=8) was administered intraperitoneally to seven-day-old rats before hypoxia-ischemia. In addition, 16 seven-day-old rats were given L-carnitine (group 3; n=8) or saline (group 4; n=8) after hypoxic ischemic insult. Apoptotic cell death was investigated by terminal dUDP-biotin nick end-labeling …(TUNEL) in all subjects following three days of recovery. In the evaluation of TUNEL- positive cells, firstly the areas (in square millimeters) of the hippocampus, striatum and cortex in the right and left hemispheres were measured by IMAGE analysis. Then the numerical density was calculated as the number of cells per square millimeter by counting all TUNEL- positive cells. Afterwards, the ratios of right side numerical density to the sum of right and left sides' numerical densities (right apoptosis index) were calculated for every brain region in rats receiving L-carnitine and they were compared with the vehicle groups. Results: The right apoptosis indexes of the hippocampus (37.4 ± 18.8; mean ± SD) and striatum (39.2 ± 15.2) in rat pups pre-treated with L-carnitine were significantly lower than those in the vehicles (59.8 ± 17.9 vs. 60.4 ± 19.6 respectively) (p< 0.05), whereas they were not changed by L-carnitine pre-treatment in the cortex. Additionally, L-carnitine post-treatment had no effect on right apoptosis indexes in any of the three brain regions. Conclusions: It is concluded that pre-treatment with L-carnitine might play a role in reducing apoptotic cell death due to neonatal hypoxic ischemic brain injury. Our results suggested that L-carnitine was useful in perinatal asphyxia for preventing hypoxic ischemic brain injury. Show more

Keywords: Apoptosis, newborn rat, hypoxia-ischemia, carnitine, regional, hippocampus, striatum, cortex

DOI: 10.3233/RNN-2010-0567

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 6, pp. 817-824, 2010

Authors: Fedorov, Anton | Chibisova, Yulia | Szymaszek, Aneta | Alexandrov, Mikhail | Gall, Carolin | Sabel, Bernhard A.

Article Type: Research Article

Abstract: Background: Recovery of post-stroke deficits can be achieved by modulating neuroplasticity with non-invasive brain stimulation. To evaluate potential effects of repetitive transorbital alternating current stimulation (rtACS) on stroke recovery we carried out a randomized, drug-controlled clinical trial. Methods: Ninety-eight patients that had suffered ischemic stroke 21.4 months earlier were randomly assigned to either group D (n=30) receiving conventional drug therapy, group ACS (n=32) treated for 12 days with rtACS, or …group D/ACS (n=36) receiving combined drug therapy/rtACS. Stroke severity level (SSL) was assessed by the NIH-NINDS stroke scale before and after treatment and at a 1-month follow-up to evaluate motor impairments (weakness, ataxia), sensory loss, visual field defects, and cortical deficits (aphasia, neglect). At each time point standard EEG recordings (10–20 system) were conducted. Results: Before therapy SSL was moderate (9.18 ± 0.78) without significant group difference (F =0.86, p=0.43). After 12 days of treatment, SSLs of groups ACS and D/ACS significantly improved by 22.5% and 25.1% over baseline, respectively, with no such change in the control group D (+3%). SSL improvements were mainly due to recovery of motor, sensory, and speech functions. After 1-month follow-up, an additional improvement of 9.7% and 9.4% was seen for the group ACS and D/ACS which led to a total change of +32.3% and +34.7% over baseline. EEG recordings revealed greater interhemispheric synchrony between both temporal lobes which were positively correlated with clinical outcome. Conclusions: Non-invasive rtACS applied to post-stroke patients can modulate brain plasticity and induce recovery from neurological deficits long after the early post lesion recovery is over. Show more

Keywords: Stroke, alternating current stimulation, recovery, aphasia, restoration

DOI: 10.3233/RNN-2010-0580

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 6, pp. 825-833, 2010