Improved Motor Function Recovery Research Articles

Effects of Chinese medicine combined with rehabilitation care on motor function recovery and quality of life in stroke paralysis patients

Objective To explore the motor function recovery and quality of life effects of Chinese medicine combined with rehabilitation care for stroke paralysis patients. Methods A total of 140 stroke paralysis patients were equally randomly divided into treatment group and control group of 70 patients, both groups were given basic treatment with conventional rehabilitation care, on the basis of the treatment group were treated with acupuncture intervention, the intervention period were 3 months. Results The overall effective rate (97.1%) in the treatment group was significantly higher than that of the control group (80.0%) (P<0.05). The neurological deficits were significantly reduced, but motor function scores were increased significantly in the two groups after the intervention that compared with pre-intervention′s (P<0.05); at the same time, the neurological deficit motor function and motor function scores in the treatment group were also significantly better than that in the control group after intervention (P<0.05). The paralysis level after the intervention, both were significantly improved, and the level of paralysis in the treatment group were significantly better than that of the control group after the intervention (P<0.05). Conclusions Chinese medicine combined with rehabilitation care for stroke paralysis patients can improve motor function and neurological deficit recovery, and promote the improvement of the overall effects. Key words: Rehabilitation nursing; Acupuncture; Stroke; Paralysis; Motor function

Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson's Disease Model.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with complicated pathophysiologic mechanisms. Endoplasmic reticulum (ER) stress appears to play a critical role in the progression of PD. We demonstrated that basic fibroblast growth factor (bFGF), as a neurotropic factor, inhibited ER stress-induced neuronal cell apoptosis and that 6-hydroxydopamine (6-OHDA)-induced ER stress was involved in the progression of PD in rats. bFGF administration improved motor function recovery, increased tyrosine hydroxylase (TH)-positive neuron survival, and upregulated the levels of neurotransmitters in PD rats. The 6-OHDA-induced ER stress response proteins were inhibited by bFGF treatment. Meanwhile, bFGF also increased expression of TH. The administration of bFGF activated the downstream signals PI3K/Akt and Erk1/2 in vivo and in vitro. Inhibition of the PI3K/Akt and Erk1/2 pathways by specific inhibitors partially reduced the protective effect of bFGF. This study provides new insight towards bFGF translational drug development for PD involving the regulation of ER stress.

Action observation training to improve motor function recovery: a systematic review.

Following the discovery of Mirror Neuron System (MNS), Action Observation Training (AOT) has become an emerging rehabilitation tool to improve motor functions both in neurologic and orthopedic pathologies.The aim of this study is to present the state of the art on the use of AOT in experimental studies to improve motor function recovery in any disease.The research was performed in PubMed, PEDro, Embase, CINAHL and Cochrane Central Register of Controlled Trials (last search July 2015). Randomized controlled trials (RCTs) that analyse efficacy of AOT for recovery of motor functions, regardless of the kind of disease, were retrieved. The validity of the included studies was assessed using the Cochrane Collaboration tool for evaluating risk of bias.Twenty RCTs were eligible. Four studies showed AOT efficacy in improving upper limb functional recovery in participants with chronic stroke, two studies in sub-acute ones and one in acute ones. Six articles suggested its effectiveness on walking performance in chronic stroke individuals, and three of them also suggested an efficacy in improving balance. The use of AOT was also recommended in individuals with Parkinson’s disease to improve autonomy in activities of daily living, to improve spontaneous movement rate of self-paced finger movements and to reduce freezing of gait. Other two studies also indicated that AOT improves upper limb motor function in children with cerebral palsy. The last two studies, showed the efficacy of AOT in improving motor recovery in postsurgical orthopedic participants. Overall methodological quality of the considered studies was medium.The majority of analyzed studies suggest the efficacy of AOT, in addition to conventional physiotherapy, to improve motor function recovery in individuals with neurological and orthopedic diseases. However, the application of AOT is very heterogeneous in terms of diseases and outcome measures assessed, which makes it difficult to reach, to date, any conclusion that might influence clinical practice.Electronic supplementary materialThe online version of this article (doi:10.1186/s40945-015-0013-x) contains supplementary material, which is available to authorized users.

Radiofrequency ablation versus magnetic resonance guided focused ultrasound surgery for minimally invasive treatment of osteoid osteoma: a propensity score matching study.

To compare outcomes in pain relief and motor functional recovery in patients with an osteoid osteoma treated by magnetic resonance guided focused ultrasound surgery (MRgFUS) or radiofrequency ablation (RFA) using a propensity score matching study design. Thirty patients with osteoid osteomas were included in this institutional review board (IRB)-approved study. MRgFUS was performed in 15 subjects. These subjects were matched by propensity analysis with a group of 15 subjects treated by RFA. Pain relief in terms of complete response (CR) and motor functional recovery were measured. A similar proportion of subjects treated by MRgFUS (94%) or RFA (100%) experienced CR 12weeks after treatment, with no significant difference. The improvement in pain control following MRgFUS or RFA paralleled with improved motor functional recovery. The treatment failure rate was 6.6% in the MRgFUS group and 0% in the RFA group. No major complications were observed following either ablative treatment. Although this study involved a limited number of patients, MRgFUS favourably improves perceived pain and motor functional recovery, with no major complications. No difference was found in the achievement of primary and secondary outcome measures with respect to RFA. • To demonstrate the effectiveness of a recent technique for treating osteoid osteoma • MRgFUS results compared with results of the gold standard treatment (RFA) • MRgFUS is effective both from a clinical and functional point of view • No significant side effects compared with RFA.

Autologous Bone Marrow Mononuclear Cells Exert Broad Effects on Short- and Long-Term Biological and Functional Outcomes in Rodents with Intracerebral Hemorrhage.

Autologous bone marrow-derived mononuclear cells (MNCs) are a potential therapy for ischemic stroke. However, the effect of MNCs in intracerebral hemorrhage (ICH) has not been fully studied. In this study, we investigated the effects of autologous MNCs in experimental ICH. ICH was induced by infusion of autologous blood into the left striatum in young and aged male Long Evans rats. Twenty-four hours after ICH, rats were randomized to receive an intravenous administration of autologous MNCs (1 × 10(7) cells/kg) or saline. We examined brain water content, various markers related to the integrity of the neurovascular unit and inflammation, neurological deficit, neuroregeneration, and brain atrophy. We found that MNC-treated young rats showed a reduction in the neurotrophil infiltration, the number of inducible nitric oxide synthase-positive cells, and the expression of inflammatory-related signalings such as the high-mobility group protein box-1, S100 calcium binding protein B, matrix metalloproteinase-9, and aquaporin 4. Ultimately, MNCs reduced brain edema in the perihematomal area compared with saline-treated animals at 3 days after ICH. Moreover, MNCs increased vessel density and migration of doublecortin-positive cells, improved motor functional recovery, spatial learning, and memory impairment, and reduced brain atrophy compared with saline-treated animals at 28 days after ICH. We also found that MNCs reduced brain edema and brain atrophy and improved spatial learning and memory in aged rats after ICH. We conclude that autologous MNCs can be safely harvested and intravenously reinfused in rodent ICH and may improve long-term structural and functional recovery after ICH. The results of this study may be applicable when considering future clinical trials testing MNCs for ICH.

Novel mGluR5 positive allosteric modulator improves functional recovery, attenuates neurodegeneration, and alters microglial polarization after experimental traumatic brain injury.

Traumatic brain injury (TBI) causes microglial activation and related neurotoxicity that contributes to chronic neurodegeneration and loss of neurological function. Selective activation of metabotropic glutamate receptor 5 (mGluR5) by the orthosteric agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), is neuroprotective in experimental models of TBI, and has potent anti-inflammatory effects in vitro. However, the therapeutic potential of CHPG is limited due to its relatively weak potency and brain permeability. Highly potent, selective and brain penetrant mGluR5 positive allosteric modulators (PAMs) have been developed and show promise as therapeutic agents. We evaluated the therapeutic potential of a novel mGluR5 PAM, VU0360172, after controlled cortical impact (CCI) in mice. Vehicle, VU0360172, or VU0360172 plus mGluR5 antagonist (MTEP), were administered systemically to CCI mice at 3 h post-injury; lesion volume, hippocampal neurodegeneration, microglial activation, and functional recovery were assessed through 28 days post-injury. Anti-inflammatory effects of VU0360172 were also examined in vitro using BV2 and primary microglia. VU0360172 treatment significantly reduced the lesion, attenuated hippocampal neurodegeneration, and improved motor function recovery after CCI. Effects were mediated by mGluR5 as co-administration of MTEP blocked the protective effects of VU0360172. VU0360172 significantly reduced CD68 and NOX2 expression in activated microglia in the cortex at 28 days post-injury, and also suppressed pro-inflammatory signaling pathways in BV2 and primary microglia. In addition, VU0360172 treatment shifted the balance between M1/M2 microglial activation states towards an M2 pro-repair phenotype. This study demonstrates that VU0360172 confers neuroprotection after experimental TBI, and suggests that mGluR5 PAMs may be promising therapeutic agents for head injury.

PARP-1 Inhibition Attenuates Neuronal Loss, Microglia Activation and Neurological Deficits after Traumatic Brain Injury

Traumatic brain injury (TBI) causes neuronal cell death as well as microglial activation and related neurotoxicity that contribute to subsequent neurological dysfunction. Poly (ADP-ribose) polymerase (PARP-1) induces neuronal cell death through activation of caspase-independent mechanisms, including release of apoptosis inducing factor (AIF), and microglial activation. Administration of PJ34, a selective PARP-1 inhibitor, reduced cell death of primary cortical neurons exposed to N-Methyl-N'-Nitro-N-Nitrosoguanidine (MNNG), a potent inducer of AIF-dependent cell death. PJ34 also attenuated lipopolysaccharide and interferon-γ-induced activation of BV2 or primary microglia, limiting NF-κB activity and iNOS expression as well as decreasing generation of reactive oxygen species and TNFα. Systemic administration of PJ34 starting as late as 24 h after controlled cortical impact resulted in improved motor function recovery in mice with TBI. Stereological analysis demonstrated that PJ34 treatment reduced the lesion volume, attenuated neuronal cell loss in the cortex and thalamus, and reduced microglial activation in the TBI cortex. PJ34 treatment did not improve cognitive performance in a Morris water maze test or reduce neuronal cell loss in the hippocampus. Overall, our data indicate that PJ34 has a significant, albeit selective, neuroprotective effect after experimental TBI, and its therapeutic effect may be from multipotential actions on neuronal cell death and neuroinflammatory pathways.

Third trimester NG2-positive amniotic fluid cells are effective in improving repair in spinal cord injury

Spinal cord injury presents a significant therapeutic challenge since the treatments available are mostly vain. The use of stem cells to treat this condition represents a promising new therapeutic strategy; therefore, a variety of stem cell treatments have been recently examined in animal models of CNS trauma.In this work, we analyzed the effects of third trimester amniotic fluid cells in a mouse model of spinal cord injury. Among the different cultures used for transplantation, some were able to induce a significant improvement in motor recovery (cultures #3.5, #3.6 and #7.30), evaluated by means of open field free locomotion. All effective cell cultures expressed the surface marker nerve/glial antigen 2, ortholog of the human chondroitin sulfate proteoglycan 4, which is present on several types of immature progenitor cells. The improved motor functional recovery was correlated with higher myelin preservation in the ventral horn white matter and an increased vascularization in the peri-lesion area. Real-Time PCR analysis showed higher expression levels of vascular endothelial growth factor and hypoxia-inducible factor-1α mRNA two days after cells transplantation compared to PBS-treated animals, indicating that an angiogenic pathway might have been activated by these cells, possibly through the production of hepatocyte growth factor. This cytokine appears to be produced mostly in filtering organs, such as the lung, of the transplanted animals and is likely released in the blood suggesting an endocrine role of hepatocyte growth factor in targeting the injury site.

Delayed administration of the nucleic acid analog 2Cl-C.OXT-A attenuates brain damage and enhances functional recovery after ischemic stroke

2Cl-C.OXT-A (COA-Cl) is a novel nucleic acid analog that enhances angiogenesis through extracellular signal-regulated kinase 1 or 2 (ERK1/2) activation. ERK1/2 is a well-known kinase that regulates cell survival, proliferation and differentiation in the central nervous system. We performed in vitro and in vivo experiments to investigate whether COA-Cl can attenuate neuronal damage and enhance recovery after brain ischemia. In primary cortical neuron cultures, COA-Cl prevented neuronal injury after 2h of oxygen-glucose deprivation. COA-Cl increased phospho-ERK levels in a dose-dependent manner and COA-Cl-induced neuroprotection and ERK1/2 activation was inhibited by suramin or PD98059. The effect of COA-Cl was evaluated in vivo with 60min of middle cerebral artery occlusion combined with bilateral common carotid artery occlusion. COA-Cl or saline was injected intracerebroventricularly 5min after reperfusion. COA-Cl significantly reduced infarct volume and improved neurological deficits upon injection of 15 or 30μg/kg COA-Cl. Moreover, COA-Cl reduced the number of TUNEL positive cells in ischemic boundary, while rCBF was not significantly changed by COA-Cl administration. We also evaluated the effect of delayed COA-Cl administration on recovery from brain ischemia by continuous administration of COA-Cl from 1 to 8 days after reperfusion. Delayed continuous COA-Cl administration also reduced infarct volume. Furthermore, COA-Cl enhanced peri-infarct angiogenesis and synaptogenesis, resulting in improved motor function recovery. Our findings demonstrate that COA-Cl exerts both neuroprotective and neurorestorative effects over a broad therapeutic time window, suggesting COA-Cl might be a novel and potent therapeutic agent for ischemic stroke.

Abstract TP97: Improved Long-Term Outcome after Transient Cerebral Ischemia in Aquaporin-4 Knockout Mice

Introduction: Aquaporin-4 (AQP4) is an abundant aquaporin in brain that has been hypothesized to play a central role in edema formation. Furthermore, AQP4 downregulation has been correlated with connexin 43 (Cx43) downregulation, a gap junction protein important for ion and water transport through astrocyte networks. AQP4 deletion in mice was shown to be beneficial at 24 hours after permanent occlusion of the middle cerebral artery (MCAO). However, the long-term consequences of AQP4 deletion on behavior, edema, and tissue properties after stroke have not been studied. Objective: Following transient MCAO, behavior, lesion volumes, blood brain barrier (BBB) integrity, neuroinflammation, and astrocyte network properties with Cx43 expressions were assessed for 14 days in wild type (WT) and AQP4 -/- mice. Methods: Transient (30-min) filament MCAO was performed on AQP4 -/- (n=5) and WT (n=8) mice on a CD1 genetic background. Behavioral outcomes were assessed by rotarod, beam balance, and foot fault tests from 1 to 14 days (d) post injury. Temporal magnetic resonance imaging (MRI) was undertaken to assess lesion volume. Mice were transcardially perfused at 15 d and the brains were extracted and frozen to perform immunohistochemical analysis for IgG, AQP4, Cx43, and glial fibrillary acidic protein (GFAP). Results: MRI showed significantly smaller lesion volume in AQP4 -/- at 1, 3, 7, and 14d. AQP4 -/- mice also had improved motor function recovery with 54% and 75% decreased number of foot-faults than WT mice respectively at 1 and 3 d; and 60% increased time spent on the rotarod compared to WT over the 14 days after stroke onset. AQP4 -/- mice had reduced IgG extravasation and Cx43 expression but increased GFAP staining compared to WT at 14d, suggesting, respectively, less BBB disruption and modified astrocyte network properties combined with altered neuroinflammation fates. Conclusion: AQP4 deletion resulted in improved long-term functional recovery associated with decreased lesion volumes and improved BBB integrity. Although more work must be done, the beneficial outcomes in AQP4 -/- may partly be due to decreased Cx43 as well, resulting in not only decreased edema formation through AQP4, but also in decreased spread of edema through the astrocyte network.

Protective effects of glucosamine-kynurenic acid after compression-induced spinal cord injury in the rat

Abstract Kynurenic acid (KYNA), a metabolite of the essential amino acid L-tryptophan, is a broad spectrum antagonist of excitatory amino acid receptors, which have also anticonvulsant and neuroprotective properties. After spinal cord injury (SCI), excitotoxicity is considered to play a significant role in the processes of secondary tissue destruction in both grey and white matter of the spinal cord. In this study, we have tested the potential therapeutic effect of glucosamine-kynurenic acid, administered after experimental compression-induced SCI in the rat. Spinal application of glucosamine-kynurenic acid continually for 24 hr after experimental SCI resulted in improved motor function recovery, beginning from the first week of evaluation and continuing until the end of the study (4 weeks). After 4 weeks’ survival, quantitative morphometric analysis of the spinal cord showed that glucosamine-kynurenic acid treatment was associated with improved tissue preservation at the lesion site. These findings indicate that spinal application of glucosaminekynurenic acid is neuroprotective and improves the outcome even when administered after spinal trauma. Our results suggest that the treatments initiated in early posttraumatic period can alleviate secondary injury and improve the final outcome after SCI.

Electrical stimulation of cerebellar fastigial nucleus promotes the expression of growth arrest and DNA damage inducible gene β and motor function recovery in cerebral ischemia/reperfusion rats

This study focused on the effects of electrical stimulation of cerebellar fastigial nucleus on the expression of growth arrest and DNA damage inducible gene β (Gadd45β) and on motor function recovery after focal cerebral ischemia/reperfusion (I/R) in rats. Sprague–Dawley (SD) rats were randomly divided into 4 groups: sham I/R (control group), I/R (I/R group), I/R with sham stimulation and I/R with electrical stimulation at 6h, 12h, 24h, 2d and 3d after I/R. Cerebral ischemia and reperfusion was established by nylon monofilament occlusion method. Fastigial nucleus (FN) electrical stimulation was applied at 2h after ischemia for 1h. The changes in the expression of Gadd45β were analyzed by immunohistochemistry, real-time polymerase chain reaction (PCR) and Western-blot respectively. Another group of rats were divided into the same 4 groups. Montoya staircase test score was used to test the motor function of affected forelimb. The levels of Gadd45β were significantly elevated after I/R injury. FN electrical stimulation treatment elevated the expression of Gadd45β further and improved motor function recovery. These results suggest that FN electrical stimulation can promote the expression of Gadd45β and motor function recovery after focal cerebral ischemia.

Differentiated adipose‐derived stem cells promote myelination and enhance functional recovery in a rat model of chronic denervation

Transplantation of autologous Schwann cells (SCs) is a promising approach for treating various peripheral nerve disorders, including chronic denervation. However, given their drawbacks, such as invasive biopsy and lengthy culture in vitro, alternative cell sources would be needed. Adipose-derived stem cells (ASCs) are a candidate, and in this study rat ASCs transdifferentiated into a SC phenotype (dASC) cocultured with dorsal root ganglion neurons were shown to associate with neurites and to express myelin basic protein (MBP)-positive myelin protein. Furthermore, dASCs transplanted into a chronically denervated rat common peroneal nerve survived for at least for 10 weeks, maintaining their differentiated state. Immunohistochemical analysis revealed that transplanted dASCs associated with regenerating axons, forming MBP-/protein zero-positive myelin sheaths. The cell survival and myelin expression assessed by double labelling with S100 and glial fibrillary acidic protein were similar between the dASC- and SC-transplanted nerves. Importantly, transplantation of dASCs resulted in dramatically improved motor functional recovery and nerve regeneration, with a level comparable to, or even superior to, transplantation of SCs. In conclusion, dASCs are capable of myelinating axons in vivo and enhancing functional outcome after chronic denervation.

FTY720 Improves Functional Recovery after Spinal Cord Injury by Primarily Nonimmunomodulatory Mechanisms

Spinal cord injury (SCI) is an incapacitating injury that can result in limited functional recovery. We have previously shown increases in the lysophospholipid mediator, sphingosine-1-phosphate (S1P), in the spinal cord after contusion injury. To apply S1P receptor modulation to the treatment of SCI, we examined the therapeutic effects of FTY720, an S1P receptor agonist, on locomotor recovery after SCI in mice. Oral administration of FTY720 shortly after contusion SCI significantly improved motor function recovery, as assessed by both Basso Mouse Scale scores and Rotarod Performance test results. FTY720 induced lymphopenia and reduced T-cell infiltration in the spinal cord after SCI but did not affect the early infiltration of neutrophils and the activation of microglia. In addition, plasma levels and mRNA expression of inflammatory cytokines in the spinal cord after SCI were not attenuated by FTY720. Vascular permeability and astrocyte accumulation were both decreased by FTY720 in the injured spinal cord. The therapeutic effects of FTY720 were not solely dependent on immune modulation, as confirmed by the demonstration that FTY720 also ameliorated motor function after SCI in mice with severe combined immunodeficiency. Finally, the S1P(1) receptor agonist, SEW2871, partly mimicked the therapeutic effect of FTY720. Our data highlight the importance of immune-independent functions of FTY720 in decreasing vascular permeability and astrogliosis in the injured spinal cord and promoting locomotor function recovery after SCI.

Metallothionein-II improves motor function recovery and increases spared tissue after spinal cord injury in rats

After spinal cord injury (SCI), a complex cascade of pathophysiological processes rapidly damages the nervous tissue. The initial damage spreads to the surrounding tissue by different mechanisms, including oxidative stress. We have recently reported that the induction of metallothionein (MT) protein is an endogenous rapid-response mechanism after SCI. Since the participation of MT in neuroprotective processes after SCI is still unknown, the aim of the present study was to evaluate the possible neuroprotective effect of exogenously administered MT-II during the acute phase after SCI in rats. Female Wistar rats weighing 200–250g were submitted to spinal cord contusion by means of a computer-controlled device (NYU impactor). Rats received several doses of MT-II (3.2, 10 and 100μg) at 2 and 8h after SCI. Results of the BBB scale were statistically analysed using an ANOVA of repeated-measures, followed by Tukey's test. Among the three doses tested, only 10 and 100μg were able to significantly increase (p<0.05) BBB scale scores eight weeks after SCI from a mean of 7.88 in the control group, to means of 12.63 and 10.88 for the 10 and 100μg doses of MT-II, respectively. The amount of spared tissue was also higher in the groups treated with 10 and 100μg, as compared to the control group values. Results from the present study demonstrate a significant neuroprotective effect of exogenously administered MT-II. Further studies are needed in order to characterize the mechanisms involved in this neuroprotective action.

Effects of intensive training on the expressions of semaphorin 3A and neuropilin-1 after cerebral ischemia-reperfusion in rats

Objective To observe the effects of intensive training at different intensities on the expressions of semaphorin 3A ( Sema 3A) and its receptor neuropilin ( NP-1 ) and the cell apoptosis in cerebrum after cerebral ischemia-reperfusion in rats,and to investigate the possible mechanism of intensive training in recovery of motor function after cerebral ischemia-reperfusion in rats. Methods To establish animal model of cerebral ischemia-reperfusion in rats,the intraluminal thread method was applied to cause left middle cerebral artery occlusion (MCAO) for 2 h and before reperfusion.After cerebral ischemia-reperfusion model were established for 24 h,60 male model Wistar rats were randomly divided into training group 1 ( swimming for 5 min once a day),training group 2 ( swimming for 10 min once a day),training group 3 (swimming for 10 min twice a day) and control group (no training) ; another 15 rats assigned to the sham-operation group were subject to no MCAO and no training.Neurological function was evaluated by Garcia scores,and terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) was performed to dectect the cortical cell apoptosis.Expressions of neural growth inhibition factor Sema 3A and its receptor NP-1 were detected by immunohistochemistry. Results The neurological function in sham-operation group was normal.The differences of Garcia scores at different time points beween sham-operation group and control group were significant (P ＜ 0.01 ).Garcia scores in all training groups,were significantly higher than those in controls at the 7th and 14th d after swimming training ( P ＜ 0.01 ),especially in training group 3 the Garcia scores were ( 12.80 ± 0.45 ),( 15.20 ± 0.45 ),( 16.80 ± 0.45 ),respectively,at the 3rd,7th and 14th d after swimming training.The rates of positive cell of Sema 3A,NP-1 and TUNEL indexes in all training groups were lower than those in controls at the 3rd,7th and 14th d after swimming training (P ＜ 0.01 ),especially in the training group 3.At the 3rd,7th and 14th d after swimming training in training group 3,the rates of TUNEL indexes positive apoptosis cells were ( 29.43 ± 1.38 ) ％,( 22.30 ± 1.21 ) ％,( 17.58 ± 1.70) ％,respectively,the positive cell rates of Sema 3A were ( 19.64 ± 1.17) ％,(9.73 ± 3.83)％,(8.24 ± 0.87)％,respectively,the positive cell rates of NP-1 were ( 33.95 ± 6.86) ％,( 27.95 ± 1.29 ) ％,( 18.90 ± 1.44 ) ％,respectively,the reduction of positive cells expressions in training group 3 was significantly more obvious compared with other training groups (P ＜ 0.01 or 0.05). Conclusions Rehabilitation training can reduce the expression of positive cell of Sema 3A,NP-1 and TUNEL indexes in rats after cerebral ischemia-reperfusion and can improve motor function recovery and facilitate neural plasticity.The more intensive the training,the better the effects. Key words: Cerebral ischemia-reperfusion ; Intensive training ; Senaphorin 3 A ; Neuropilin-1 ; Cell apoptosis

AAV-mediated netrin-1 overexpression increases peri-infarct blood vessel density and improves motor function recovery after experimental stroke

Apart from its role in axon guidance, netrin-1 is also known to be pro-angiogenic. The aim of this study is to determine whether adeno-associated viral (AAV) mediated overexpression of netrin-1 improves post-stroke neurovascular structure and recovery of function. AAV-Netrin-1 or AAV-LacZ of 1 × 10 10 genome copies each was injected medial and posterior to ischemic lesion at one hour following reperfusion using the distal middle cerebral artery occlusion (MCAO) method. Quantitative RT-PCR revealed that the expression of netrin-1 transgene began as early as one day and increased dramatically about 3 weeks following vector injection. Western blot analysis and confocal microscopy suggested that both the endogenous and transduced netrin-1 were expressed in the neurons of the peri-infarct cortex after MCAO. AAV-mediated netrin-1 overexpression significantly increased vascular density in the peri-infarct cortex and promoted the migration of immature neurons into the peri-infarct white matter, but it did not significantly reduce infarct size. Netrin-1 overexpression also enhanced post-stroke locomotor activity, improved exploratory behavior, and reduced ischemia-induced motor asymmetry in forelimb usage. However, it had little effect on post-stroke spatial learning and memory. Our results suggest that AAV mediated netrin-1 overexpression improves peri-infarct vascular density and post stroke motor function.

The effects of citicoline combined with rehabilitative training on neural plasticity after focal cerebral ischemia

Objective To investigate the effects of citicoline combined with rehabilitative training on motor function after focal cerebral ischemia. Methods One hundred and twenty male adult Sprague-Dawley rats ( 3 months old) were subjected to left middle cerebral artery occlusion (MCAO) by suturing. Ninety-six of them were randomly divided into four groups of 24: a control group, a drug group, a rehabilitative training group, and a drug combined with rehabilitative training group. The rats in the control group did not receive any treatment. Three days after reperfusion, those in the drug group received 500 mg/kg of citicoline daily; those in the rehabilitative training group received motor training including balancing, grasping, rotating and walking exercises; those in the combined group received both citicoline and the motor training program. Behavioral tests were administered at the 7th, 14th and 21st days after MCAO. At the same time points, immunohistochemistry was used to detect calcium-binding protein S100 and β-tubulin expression in the peri-ischemia region of the cortex. Results ①As compared with the control group, the drug group at the 7th, 14th and 21st day after MCAO and the other two groups at the 7th day after MCAO showed no significant difference in average behavior scores. But at the 14th and 21st day the rehabilitative training group as well as the drug combined with rehabilitative training group had average behavior scores significantly superior to those of the control group, especially in the drug combined with rehabilitative training group. ②As compared with the control group, the expression of S100 and β-tubulin in the drug and rehabilitative training groups at the 7th day after MCAO showed no significant difference. In the drug combined with rehabilitative training group the average score was significantly higher than in the other groups at the 7th day after MCAO. All the other groups had average scores significantly higher than that of the controls at the 14th and 21st day after MCAO, especially the drug combined with rehabilitative training group. Conclusions Citicoline combined with rehabilitative training can significantly improve motor function recovery in rats. The effect of the combined modalities was more obvious, and the functional enhancement might be partially attributable to the up-regulation of S100 and β-tubulin in the cortex. Key words: Cerebral ischemia; Citicoline; Rehabilitative training; Calcium-binding protein; β-tubulin

Reappraisal of Methylprednisolone Treatment for Acute Traumatic Cord Injury

Objective: The value of methylprednisolone (MP) treatment in acute traumatic spinal cord injury (SCI) remains controversial. We attempted to evaluate the utilization of resources, motor function recovery and adverse effect after the use of MP. Methods: We compared 13 demographic and clinical characteristics between MP and non-MP treatment groups in 110 patients with acute traumatic SCI treated in hospitals between June 1st, 2000 and May 31st, 2001, and analyzed 10 short-term outcome variables. These demographic and clinical characteristics included age, cause of injury, number of associated injuries, Revised Trauma Score, Glasgow Coma Scale, mean blood pressure, level/completeness and pattern of SCI, number and types of spinal surgeries, frequency of rehabilitation therapy and the time interval between trauma and admission. Results: The MP (64.5%) and non-MP (35.5%) treatment groups showed no significant differences in all characteristics except the time interval between trauma and admission (P=0.024). MP treatment was associated with a higher frequency of infectious complications (P=0.038), but there was no difference between the two treatment groups in other outcome parameters. The results of analysis stratified by dosage of MP showed that the length of ICU stay (P=0.021) and the number of tracheostomies (P=0.005) and pneumonia cases (P=0.004) were increased significantly in the standard dose group. Conclusions: Although the rate of infection had risen in patients receiving MP, the steroid treatment did not significantly increase utilization of resources during hospitalization and appeared safe in terms of mortality. However, it had not been proven to improve motor function recovery.

On the move to stimulate cell plasticity in the substantia nigra in Parkinson's disease

Background. Parkinson's disease (PD) is the second mostcommon neurodegenerative disorder affecting over 1% ofindividuals over 50 years of age. A major neuropathologicalfeature to PD is the progressive degeneration of dopaminergicneurons in substantia nigra leading to a dramatic reduction ofdopamine levels in the striatum. The study by Steiner andcoworkers published in this issue of Experimental Neurology(Steiner et al., this issue) examined functional and morpholog-ical effects of housing rats with unilateral neurotoxin-inducedlesions of the nigrostriatal pathway in an enriched environmentinvolving physical activity. Enriched environment typicallyinvolves housing rodents in large groups with access toappealing “toys”, e.g., ladders, tubes and boxes. The additionalphysical activity consisted of the rats walking on a rotarod for10–20minonce daily(Steineretal., thisissue).Inthe unilateralrat model of PD, a combination of altered housing conditionsand daily physical activity induced an increase in the number ofbromodeoxyuridine (BrdU)-labeled, newborn cells in thesubstantia nigra. The lesion itself, induced by intrastriatalinjections of the neurotoxin 6-hydroxydopamine, did not affectthe rate of cell proliferation in the substantia nigra, which is atvariance with some earlier studies that have reported increasesfollowing nigral lesions (Kay and Blum, 2000; Mohapel et al.,2005; Shan et al., 2006; Zhao et al., 2003). The majority of theBrdU-positive, newborn cells were also positive for NG2, glialfibrillary acid protein (GFAP) or the microglial marker Iba1.The chondroitin sulfate proteoglycan NG2 is expressed on thesurface of neural cells whose role in the brain is not fullyestablished. The NG2 positive cells have been called “poly-dendrocytes” (Nishiyama et al., 2002) and have also beensuggestedtobeoligodendrocyteprecursors.In contrast, noneofthe newborn, BrdU-stained cells in the substantia nigraexpressed the markers for neuroblasts and neurons that werestudied, i.e., doublecortin, NeuN and tyrosine hydroxylase.Around one third of the BrdU-labeled cells were not labeled byany of the phenotype-specific markers that were examined.Earlier studies have reported the occurrence of angiogenesis inthe substantia nigra following dopamine-denervating lesions(Barcia et al., 2005; Carvey et al., 2005). It is therefore possiblethat newborn cells with an unidentified phenotype were ofvascular origin, although endothelial markers were not exa-mined in this study. Steiner and collaborators also report thatenriched environment combined with physical activity im-proves recovery of motor function in one of the studied groups.Their conclusion is based on that there was a significant re-duction in amphetamine-induced rotation in rats studied after 7weeks compared to a similar group tested at 4 weeks after le-sion, and that the difference was only significant in rats sub-jected to exercise in combination with enriched environment.This behavioral recovery was not, however, striking. Also therats housed under normal conditions exhibited a trend forspontaneous normalization of rotational asymmetry between 4and7weekspost-lesion (seeFig.2in(Steineret al.,this issue)).Therefore, despite the clearly significant changes in cellularplasticity in the substantia nigra, there was not a clearly signi-ficant impact of the housing conditions and physical activity onfunctional recoveryofthelesion-induceddeficits asassessedbyrotational behavior. Further studies using behavioral tests thatdo not involve drug treatment (e.g., spontaneous rotation,forelimb use for stepping or reaching) may help to determinewhether the enriched environmental conditions employed by