Restorative neurology and neuroscience (RESTOR NEUROL NEUROS )

Publisher: IOS Press

Description

The journal is interdisciplinary. Papers relating the plasticity and response of the nervous system to accidental of experimental injuries or in-terventions, transplantation, neurodegenerative disorders, and experimental strategies to improve regeneration or functional recovery will be considered for publication. Experimental and clinical research papers adopting fresh conceptual approaches are encouraged. The overriding criteria for publication are novelty, significant experimental or clinical relevance, and interest to a multidisciplinary audience. Experiments on unanesthetized animals should conform with the standards for the use of laboratory animals as established by the Institute of Laboratory Animal Resources, US National Academy of Sciences. Experiments in which paralytic agents are used must be justified. Patient identity should be concealed. All manuscripts are sent out for blind "peer review" to editorial board members or outside reviewers.

Impact factor 4.18

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    Impact factor
  • 5-year impact
    3.41
  • Cited half-life
    5.40
  • Immediacy index
    0.42
  • Eigenfactor
    0.00
  • Article influence
    1.10
  • Website
    Restorative Neurology and Neuroscience website
  • Other titles
    Restorative neurology and neuroscience (Online)
  • ISSN
    0922-6028
  • OCLC
    47094437
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

IOS Press

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • On author's personal website, institutional website or funder's website, including PubMed Central
    • Non-commercial use only
    • Publisher copyright and source must be acknowledged
    • Author's version can be used
    • Publisher's pdf can be used on institutional website, company website or funding agency website for a fee
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Acute hypobaric hypoxia (HH) causes persistent cognitive impairment, affecting memory function specifically. Mitochondrial dysfunction and synaptic morphological change were the prominent pathological features of HH exposure on brain. Quercetin, a flavonoid found in fruits, vegetables, leaves and grains, is reported to prevent ischemia induced by neuronal injury. This study investigated the efficacy of quercetin to ameliorate HH-induced memory deficit. Methods: Rats were exposed to HH equivalent to 5000 m for 7 days in a decompression chamber and received quercetin daily (50, 75 or 100 mg/kg·bw) via gavage during the period of exposure. Cognitive performance was assessed by the Morris water maze test. In vitro, the effect of quercetin was tested in hippocampus tissue. Results: Quercetin, especially at 100 mg/kg·bw, significantlyreduced HH-induced memory decline. Meanwhile, HH-induced hippocampus mitochondrial and synaptic lesions were ameliorated by quercetin. Furthermore, quercetin regulated the expression of sirtuin 1(Sirt1), PGC-1α, and the proteins related with mitochondrial biogenesis and dynamics. Moreover, quercetin increased expression of fibronectin type III domain-containing protein 5 (FNDC5) and brain-derived neurotrophic factor (BDNF), showing the PGC-1α/FNDC5/BNDF pathways might be involved in neuronal adaptation. Conclusions: The results suggest quercetin has prophylactic potential for amelioration of HH-induced memory impairment, which is associated with the mitochondrial and neuronal adaptation in hippocampus.
    Restorative neurology and neuroscience 01/2015;
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    ABSTRACT: Purpose: To investigate whether prefrontal cortex (PFC) functioning during ataxic gait is linked to compensatory mechanisms or to the typical intra-subject variability of the ataxic gait. Methods: Nineteen patients with chronic ataxia and fifteen healthy subjects were evaluated. The subjects were requested to walk along a straight distance of 10 meters while PFC oxygenation and gait parameters were assessed. PFC activity was evaluated by NIRO-200 while gait analysis was performed by the SMART-D500. To investigate the intra-subject variability of gait, we calculated the coefficient of multiple correlation (CMC) of the hip, knee and ankle kinematic waveforms furthermore, we evaluated the step width. Results: We observed a positive correlation between PFC bilateral oxygenation changes and the step width (r = 0.54; p = 0.02 for the right PFC, and r = 0.50; p = 0.03 for the left PFC). No correlation was found between PFC activity and CMC of the hip, knee and ankle waveforms. Conclusions: Our results suggest that PFC activity is linked to gait compensatory mechanisms more than to the variability of the joint kinematic parameters caused by a defective cerebellar control.
    Restorative neurology and neuroscience 01/2015;
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    ABSTRACT: Purpose: To investigate the neurologic and functional effect of intracordal hyaluronate injections in acute unilateral vocal fold paralysis (UVFP) in a randomized controlled trial. Methods: In this open-label, randomized controlled study, 29 patients with UVFP were recruited within 6 months of their first outpatient visit and were randomized to receive either single hyaluronate injection (HI group) or conservative management (CM group). Quantitative laryngeal electromyography, videolaryngostroboscopy, UVFP-related quality of life (Voice Outcomes Survey, VOS), laboratory voice analysis, and health-related quality of life (SF-36) were evaluated at baseline, and at 1, 3 and 6 months post-injection in the HI group, and at baseline and 6 months in the CM group. Results: Improvements in most quality of life domains and other assessments were comparable between the HI and CM groups; however, the HI group had a greater improvement in the mental health domain of quality of life at the end of follow-up. Conclusions: Early hyaluronate injection cannot improve nerve regeneration but can result in long-lasting improvements in patients' psychosocial well-being, thus highlighting the importance of early intervention for patients with UVFP.
    Restorative neurology and neuroscience 01/2015;
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    ABSTRACT: Purpose: The present work compared the behavioral outcomes of ACCS therapy delivered either intravenously (i.v.) or intracerebroventricularly (i.c.v.) after penetrating ballistic-like brain injury (PBBI). Histological markers for neuroinflammation and neurodegeneration were employed to investigate the potential therapeutic mechanism of ACCS. Methods: Experiment-1, ACCS was administered either i.v. or i.c.v. for 1 week post-PBBI. Outcome metrics included behavioral (rotarod and Morris water maze) and gross morphological assessments. Experiment-2, rats received ACCS i.c.v for either 1 or 2 weeks post-PBBI. The inflammatory response was determined by immunohistochemistry for neutrophils and microglia reactivity. Neurodegeneration was visualized using silver staining. Results: Both i.v. and i.c.v. delivery of ACCS improved motor outcome but failed to improve cognitive outcome or tissue sparing. Importantly, only i.c.v. ACCS treatment produced persistent motor improvements at a later endpoint. The i.c.v. ACCS treatment significantly reduced PBBI-induced increase in myeloperoxidase (MPO) and ionized calcium binding adaptor molecule 1 (Iba1) expression. Concomitant reduction of both Iba1 and silver staining were detected in corpus callosum with i.c.v. ACCS treatment. Conclusions: ACCS, as a treatment for TBI, showed promise with regard to functional (motor) recovery and demonstrated strong capability to modulate neuroinflammatory responses that may underline functional recovery. However, the majority of beneficial effects appear restricted to the i.c.v. route of ACCS delivery, which warrants future studies examining delivery routes (e.g. intranasal delivery) which are more clinically viable for the treatment of TBI.
    Restorative neurology and neuroscience 01/2015;
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    ABSTRACT: Purpose: Transcranial electric stimulations (tES) with amplitude-modulated currents are promising tools to enhance neuromodulation effects. It is essential to select the correct cortical targets and inhibitory/excitatory protocols to reverse changes in specific networks. We aimed at assessing the dependence of cortical excitability changes on the current amplitude of 20 Hz transcranial alternating current stimulation (tACS) over the bilateral primary motor cortex. Methods: We chose two amplitude ranges of the stimulations, around 25 μA/cm2 and 63 μA/cm2 from peak to peak, with three values (at steps of about 2.5%) around each, to generate, respectively, inhibitory and excitatory effects of the primary motor cortex. We checked such changes online through transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs). Results: Cortical excitability changes depended upon current density (p = 0.001). Low current densities decreased MEP amplitudes (inhibition) while high current densities increased them (excitation). Conclusions: tACS targeting bilateral homologous cortical areas can induce online inhibition or excitation as a function of the current density.
    Restorative neurology and neuroscience 01/2015;
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    ABSTRACT: Purpose: We aimed to develop a nonhuman primate (NHP) stroke model for studies of secondary lesions in remote areas and to characterize its behavioral and neuroimaging features. Methods: Monkeys were either subjected to middle cerebral artery occlusion (MCAO) distal to the M1 branch (n = 17) or sham operation (n = 7). Neurological assessment and magnetic resonance imaging (MRI) were performed before and 1 week after operation. Results: After MCAO, six monkeys showed occlusion of the distal M1 segment and infarcts predominantly in the cortical and subcortical regions, without hippocampal and thalamic involvement. They had obvious neurological deficits. The other 11 monkeys showed blockage of the main trunk of the MCA, with infarcts extending into the hippocampus and thalamus, but no substantia nigra involvement. Their infarct volume were larger and neurological deficits were more severe than those after distal M1 occlusion. All sham-operated monkeys displayed normal behavior; however, MRI revealed small infarcts in three animals. Conclusions: MCAO or even sham operations might cause cerebral infarction in NHPs. Therefore, neurological assessment should be combined with MRI for screening candidate stroke models. Our model is suitable for studying secondary damage in remote regions, including the thalamus, hippocampus, and substantia nigra, after stroke.
    Restorative neurology and neuroscience 01/2015;
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    ABSTRACT: Purpose: L-dopa has been shown to improve outcome of moderate-intensity language training after stroke in acute aphasia. Given the critical role of training intensity we probed the effect of l-dopa in combination with high-intensity language training in chronic post-stroke aphasia. Methods: In this prospective, randomized, placebo-controlled, double-blind study, aphasia patients (>1 year post stroke) were administered 100/25 mg of l-dopa/carbidopa or placebo daily prior to four hours of language training for two weeks. Conditions were crossed-over after a wash-out period of 4 weeks. Results: An a-priori planned interim analysis (n = 10) showed that naming performance and verbal communication improved significantly and persistently for at least 6 months in every patient, but l-dopa had no incremental effect to intensive training. Conclusion: High-intensity language training in chronic aphasia may take learning to a ceiling that precludes additive benefits from l-dopa. Effects of l-dopa on post-stroke recovery during less intense treatment in chronic aphasia remain to be evaluated.
    Restorative neurology and neuroscience 01/2015;
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    ABSTRACT: Purpose: Vision loss after traumatic optic nerve injury is considered irreversible because of the retrograde loss of retinal ganglion cells (RGCs) which undergo apoptosis. Because the second messenger caspase-3 plays a major role in apoptosis, we now evaluated the efficacy of the specific caspase-3 inhibitor, Z-DEVD-FMK, in a rabbit model of fluid percussion injury (FPI) which mimics traumatic optic nerve injury in humans to enhance cell survival and improve vision. Methods: Survival of RGCs and recovery of vision were studied using retinal morphological markers and visual evoked potentials (VEP), respectively. The FPI traumatized animals were treated in their right eye with a single intravitreal or peribulbar injection of Z-DEVD-FMK 30 min post-injury compared to 2% DMSO control injections in their left eye. Results: Intravitreal Z-DEVD-FMK, but not control injections, led to down-regulation of capase-3 and reduced, in a dose-dependent manner, RGCs apoptosis from 7 to 21 days post-injury. These morphological improvements were accompanied by vision restoration as documented by VEP. The neuroprotection after intravitreal injection of Z-DEVD-FMK was more effective than the peribulbar application. Conclusions: The caspase-3 inhibitor Z-DEVD-FMK is neuroprotective by inhibiting RGCs apoptosis when injected 30 min after optic nerve damage and significantly promotes restoration of vision. A controlled clinical trial is now needed to evaluate the efficacy and safety of Z-DEVD-FMK in humans.
    Restorative neurology and neuroscience 01/2015;
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    ABSTRACT: Purpose: Disorders of consciousness (DOC) diagnosis relies on the presence or absence of purposeful motor responsiveness, which characterizes the minimally conscious state (MCS) and the unresponsive wakefulness syndrome (UWS), respectively. Functional neuroimaging studies have raised the question of possible residual conscious awareness also in clinically-defined UWS patients. The aim of our study was to identify electrophysiological parameters, by means of a transcranial magnetic stimulation approach, which might potentially express the presence of residual networks sustaining fragmentary behavioral patterns, even when no conscious behavior can be observed. Methods: We enrolled 25 severe DOC patients, following post-anoxic or traumatic brain injury and 20 healthy individuals (HC) as control group. Baseline electrophysiological evaluation evidenced, in comparison to HC, a partial preservation of cortical effective connectivity and excitability in clinically defined MCS, whereas these components were absent in clinically defined UWS. Then, we applied an anodal transcranial direct current stimulation (a-tDCS) protocol over the orbitofrontal cortex. Result: a-tDCS was able to boost cortical connectivity and excitability in all HC, MCS, and to unmask such excitability/connectivity in some UWS patients. Conclusion: a-tDCS could be useful in identifying residual connectivity markers in clinically-defined UWS, who may lack of purposeful behavior as a result of a motor-output failure.
    Restorative neurology and neuroscience 01/2015;
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    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.
    Restorative neurology and neuroscience 12/2014;
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    ABSTRACT: Purpose: Transcranial magnetic stimulation (TMS) and measurements of upper limb function were longitudinally applied to gain further insights into processes involved in functional recovery from the acute to the chronic stage after stroke. Methods: 10 acute stroke patients were monitored over 6 months behaviourally and with established TMS protocols. By using neuronavigated motor mapping, behavioural sparameters, and a mixed model analysis, the role of the frontal and parietal part of the motor area of both hemispheres for functional recovery was determined. Results: Size and volume of the ipsilesional motor area (MAipsi) were significantly decreased in the acute phase compared to the contralesional motor area (MAcontra). Size of MAipsi, especially its frontal part, changed over time and was positively correlated with functional recovery, whereas resting motor threshold, volume of both MA or the shift of its center of gravity did not show any association with recovery. Conclusion: The present data suggests the presence of a positive correlation between changes of the motor representation of the lesioned hemisphere and functional recovery after stroke. A possible interpretation is that rather (re-)activated corticomotor outputs are substrates of functional recovery after stroke than increased efficacy of residual, non-lesioned pathways.
    Restorative neurology and neuroscience 12/2014;
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    ABSTRACT: Purpose: Based on several positive effects of whole-body-vibration (WBV) therapy on recovery after SCI, we looked for correlations between functional (analysis of locomotion), electrophysiological (H-reflex) and morphological (density of functioning capillaries) measurements after SCI and WBV-treatment. Methods: Severe compression SCI at low-thoracic level (T8) in adult female Wistar rats was followed by WBV twice a day (2 × WBV) over a 12-week post-injury period. Intact rats and rats with SCI but no WBV-therapy ("No-WBV") served as controls. Recovery of locomotion was determined by BBB-locomotor rating, foot stepping angle (FSA), rump-height index (RHI), correct ladder steps (CLS) and H-reflex at 1, 3, 6, 9, and 12 weeks after SCI. Animals were sacrificed by an overdose of Isoflurane (Abbott). One hour later their spinal cords were fixed in 4% PFA for 24 h. Samples from the thoracic cord containing the lesion site and from the lumbar intumescence were cut into 10 μm thick longitudinal frozen sections. Results: All functioning capillaries were unequivocally identified because the endogenous peroxidase of the erythrocytes was clearly visualized with 0.05% diaminobenzidine (DAB). A determination of their absolute (in μm2) and proportional areas (percent of photographed tissue) revealed a significantly denser capillary network in the WBV-treated rats: 1,66 ± 0,41% in the "vibrated" rats versus 0,79 ± 0,19% in the "No-WBV" animals. The portion of the capillary network in intact rats was 1,51 ± 0,69%. Surprisingly, even though the vascularization in the treated animals was significantly increased, this had no beneficial influence on the recovery of functions after SCI. Conclusion: The results of this study provide for the first time evidence that intensive WBV-therapy leads to a significantly denser capillary network in the lesioned spinal cord. However, since this higher capillary density is not associated with improved functional recovery (possibly because it exceeded the balance necessary for functional improvements), optional treatments with lower intensity or less time of WBV-therapy should be tested.
    Restorative neurology and neuroscience 12/2014;
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    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.
    Restorative neurology and neuroscience 11/2014;
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    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.
    Restorative neurology and neuroscience 11/2014;
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    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.
    Restorative neurology and neuroscience 11/2014;
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    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.
    Restorative neurology and neuroscience 11/2014;
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    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.
    Restorative neurology and neuroscience 10/2014;
  • Restorative neurology and neuroscience 09/2014;