Objective:To discuss whether the alteration of neurological impairment of rats with cerebral infarction after the treatment of functional electrical stimulation(FES) was relevant to the phosphorylation of glycogen synthase kinase-3β(GSK-3β) in their ischemic penumbra fields.Method:Totally 72 rats were randomly divided into three groups:sham-operation,control and NMES treatment.They were subdivided into 4 subgroups,0-day(before treatment),3-day,7-day,14-day treatments,and 6 rats in each.Cerebral infarction was achieved by the permanent middle cerebral artery occlusion(pMCAO).NMES treatment with hypodermic electrodes was provided once per day and 30 min per time.Modified neurological severity score (mNSS) and phosphorylation of GSK-3 in brain were assessed at each observation point.Result:For the mNSS points and comparing with the control group,the improvement of neurological function was observed among rats treated for 7 and 14 days (P＜0.05),but not in 3 days treatment.As the phosphorylation of GSK-3β in the rats penumbra field,it is higher in control group and NMES group than those in sham operation group,and the highest is the 7days treatment group.Conclusion:NMES can ameliorate the neurological impairment after cerebral infarction,and its mechanism involves elevating the phosphorylation of GSK-3β.

BACKGROUND The role of nicotinic acetylcholine receptor alpha7 subunit (a7nAchR) in the treatment of acute cerebral ischemia by VNS has not been thoroughly clarified to date. Therefore, this study aimed to investigate the specific role of a7nAchR and explore whether this process is involved in the mechanisms of VNS-induced neuroprotection in rats undergoing permanent middle cerebral artery occlusion (PMCAO) surgery. MATERIAL AND METHODS Rats received a7nAChR antagonist (A) or antagonist placebo injection for control (AC), followed by PMCAO and VNS treatment, whereas the a7nAChR agonist (P) was utilized singly without VNS treatment but only with PMCAO pretreatment. The rats were randomly divided into 6 groups: sham PMCAO, PMCAO, PMCAO+VNS, PMCAO+VNS+A, PMCAO+VNS+AC, and PMCAO+P. Neurological function and cerebral infarct volume were measured to evaluate the level of brain injury at 24 h after PMCAO or PMCAO-sham. Moreover, the related proteins levels of a7nAChR, p-JAK2, and p-STAT3 in the ischemic penumbra were assessed by Western blot analysis. RESULTS Rats pretreated with VNS had significantly improved neurological function and reduced cerebral infarct volume after PMCAO injury (p<0.05). In addition, VNS enhanced the levels of a7nAchR, p-JAK2, and p-STAT3 in the ischemic penumbra (p<0.05). However, inhibition of a7nAchR not only attenuated the beneficial neuroprotective effects induced by VNS, but also decreased levels of p-JAK2 and p-STAT3. Strikingly, pharmacological activation of a7nAchR can partially substitute for VNS-induced beneficial neurological protection. CONCLUSIONS These results suggest that a7nAchR is a pivotal mediator of VNS-induced neuroprotective effects on PMCAO injury, which may be related to suppressed inflammation via activation of the a7nAchR/JAK2 anti-inflammatory pathway.

Objective To study the effects of different types of exercise training on learning and memory, as well as on the expression of synaptophysin (SYP) and on postsynaptic density protein 95 (PSD-95) in rats in which a model of vascular dementia had been created.Methods Forty male Wistar rats were divided randomly into a voluntary exercise group (V-EX) , a forced exercise group (F-EX) , an involuntary exercise group (I-EX) , a vascular dementia group (VD) and a sham-operation group (Sham) , with 8 rats in each group.Two-vessel occlusion (2-VO) of the arteria carotis communis was used to create a model of vascular dementia in all of the rats except those in the sham-operation group.Beginning one week after the surgery, the V-Ex rats were free to run in a running wheel.The F-EX rats were forced to run 270 m a day in an electric wheel.The I-EX rats were stimulated to imitate the gait pattern of their forelimbs running at 9 m/min three times a day for l0 minutes each time.No special training was given to the rats in the other 2 groups.Three weeks after the surgery, their learning and memory were tested using a novel object recognition test.Immediately after the test, their prefrontal cortex was sampled and the expression of SYP and PSD-95 was detected using western blotting.Results The average novel object recognition indices of the rats in the V-EX, F-EX and I-EX groups were all significantly higher than that of the VD group.Average PSD-95 expression was also significandy higher than in the VD group.Conclusion Exercise, whether voluntary, forced or induced by functional electrical stimulation can improve learning and memory in vascular dementia, at least in rats.The mechanism is possibly that the training can increase the expression of PSD-95 in the prefrontal cortex, though not SYP.

A rat model of vascular dementia was used to compare the effects of involuntary exercise induced by functional electrical stimulation (FES), forced exercise and voluntary exercise on the recovery of cognitive function recovery and its underlying mechanisms. In an involuntary exercise (I-EX) group, FES was used to induce involuntary gait-like running on ladder at 12 m/min. A forced exercise group (F-EX) and a voluntary exercise group (V-EX) exercised by wheel running. The Barnes maze was used for behavioral assessment. Brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase 1 and 2 (ERK1/2) and cAMP response element binding protein (CREB) positive cells in hippocampal CA1, CA2/3 and dentate gyrus (DG) regions were evaluated using immunohistochemical methods. Western blotting was used to assess the levels of BDNF, phosphorylated protein kinase B (Akt), tropomyosin receptor kinase B (TrkB), mitogen-activated protein kinase 1 and 2 (MEK1/2), ERK1/2 and CREB in BDNF-pCREB signaling in the hippocampus and prefrontal cortex. Involuntary, forced and voluntary exercises were all found to reverse the cognitive deficits of vascular dementia with about equal effectiveness. The number of BDNF, pCREB and pERK1/2 immunopositive cells was significantly increased in the hippocampal CA1, CA2/3 and DG regions in all three exercise groups. In addition, involuntary exercise activated BDNF and the phosphorylation of Akt, TrkB, MEK1/2, ERK1/2 and CREB in the hippocampus and prefrontal cortex equally as well as voluntary or forced exercise. These results suggest that involuntary exercise induced by FES may be as beneficial for alleviating cognitive deficits after cerebral ischemia.

Objective To investigate whether functional electrical stimulation (FES) can improve the expression of proteins in the NMDAR1-pGLuR1 pathway so as to promote the recovery of motor function and sensation after stroke.Methods Eighty-one Wistar rats were used to make a photochemical brain model of local ischemia.Rats were randomly assigned into a sham, placebo stimulation or FES group.Rats in the placebo and FES groups had local ischemia induced in the M1 zone of the brain using the photosensitive dye Bengal rose.It was administered intravenously and a laser beam was then stereotactically positioned on the skull.The rats in the FES groups were stimulated for 30 minutes (10 minutes on, 10 minutes off, then 10 minutes on).The placebo group's treatment was similar, but without the electric current.The rats in the sham group received no intervention.The cylinder test and the adhesive-removal test were used to test the rats' motor function and sensation before the operation and before they were sacrificed.Cohorts were sacrificed after 3, 7 and 14 days of intervention.NMDA receptor and AMPA receptor were detected in the peri-ischemic cortex using western blotting.Results After 7 and 14 days the index of forelimb motor function in the cylinder test of the FES group was significantly better than that of the placebo group.The average adhesive-removal time of the FES group was also significantly faster compared with the placebo group.After 7 days the average expression of NMDAR1 in the FES group was significantly higher than in the placebo group.The average expression of GluR1 and pGluR1 in the FES group was significantly higher than in the placebo group after 14 days.Conclusion Functional electrical stimulation can improve motor function after ischemia through the NMDARAMPAR signal pathway, at least in rats.