Objective To determine the effect of activating parvalbumin (PV) positive inhibitory neurons on memory impairment caused by frontal cortex ischemia and analyze the related mechanism. Methods Adult PV-Cre mice were randomly divided into control group [frontal cortex injection of 0.9% NaCl+ intraperitoneal injection of clozapine N-oxide hydrochloride (CNO)], model group (frontal cortex injection of endothelin+intraperitoneal injection of 0.9% NaCl) and intervention group (prefrontal cortex injection of endothelin+intraperitoneal injection of CNO). Among them, virus microinjection technology was adopted to specifically express mCherry in the PV neurons in the frontal cortex of mice from the control group, while specifically express hM3d-mCherry in the PV neurons from the model group and the intervention group. Injection of CNO was performed in the intervention group to specifically activate PV positive neurons through hM3d. The memory and motor functions of mice were detected by T-maze and object location and recognition tasks. The changes of dendritic spine density of pyramidal neurons in frontal cortex were analyzed by Golgi staining. Results The administration of endothelin in frontal cortex caused local ischemia. Compared with the normal control group, the density of dendritic spines on pyramidal neurons was decreased after frontal cortex ischemia, resulting in the decrease of selection accuracy in T-maze and exploration scores in object location and recognition tasks (P < 0.01). On the contrary, activation of PV positive neurons significantly increased the density of dendritic spines in frontal cortex, and significantly improved the selection accuracy of mice in T-maze test (P < 0.05) and the exploration score in object location and recognition tasks (P < 0.05). Conclusion Activation of PV positive neurons can improve memory impairment caused by frontal cortex ischemia, which may be related to increasing the density of dendritic spines in frontal cortex.

Objective To explore the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on the motor function, proliferation and differentiation of oligodendrocyte precursor cells (OPC), and expression of oligodendrocyte transcription factor 1 (Olig1), myelin basic protein (MBP) and NG2 in the striatum of rats after focal cerebral ischemia. Methods Sixty-three adult male SPF Sprague-Dawley (SD) rats were randomly divided into model group, rTMS group, and sham group, with 21 rats in each group. Transient middle cerebral artery embolism (tMCAO) model was prepared by thread embolization in the model group and rTMS group. Subsequently, the model group recovered naturally without any intervention, while the rTMS group received high frequency rTMS treatment every 24 h for 10 d. Each group was further assigned into 7 rats at the time points of days 1, 3, and 10 postoperatively, and modified neurological severity score (mNSS) was used to evaluate the motor function of the rats. Then the brains of each group were taken out for further analyses. Immunohistochemical staining was performed to observe the expression of NG2 and MBP in the ischemic striatum to evaluate the proliferation of OPC and severity of myelin damage. Western blotting was adopted to detect the expression of Olig1, MBP, and NG2 in the ischemic striatum. Results rTMS treatment significantly reduced the mNSS of tMCAO rats, with lower score in the rTMS group than in the model group (P < 0.05); It also promoted the proliferation and differentiation of OPC in tMCAO rats, which presented as a higher level of NG2 in the rTMS group than in the model group on days 1, 3 and 10 postoperatively (P < 0.05), as well as a higher level of Olig1 on days 3 and 10 (P < 0.05). In addition, although MBP expression in the model group was consistently lower than that in the sham group (P < 0.05), the level was higher in the rTMS group than the model group on day 10 (P < 0.05), suggesting that rTMS also promoted the repair of myelin sheath after cerebral ischemia. Conclusion Application of high-frequency rTMS can promote OPC proliferation and myelin repair in the acute phase of post-ischemic stroke.

Prefrontal ischemia can cause impairments in learning and memory, executive functions and cognitive flexibility. However, the related cellular mechanisms at the early stage are still elusive. The present study used ischemic stroke in medial prefrontal cortex and systemically investigated the electrophysiological changes of the parvalbumin (PV+) interneurons 12 h post ischemia. We found that Ih and the related voltage sags in PV+ interneurons are downregulated post ischemia, which correlates with hyperpolarization of the membrane potentials and increased input resistance in these interneurons. Consistent with the suppression of Ih, postischemic PV+ interneurons exhibited a reduction in excitability and exerted a less inhibitory control over the neighboring pyramidal excitatory neurons. Moreover, we found that specifically chemogenetic activation of PV+ neurons at early stage ameliorated prefrontal ischemia-induced spatial working memory dysfunction in T-maze without effects on the locomotor coordination and balance. In contrast, suppression of PV+ neurons by blockade of Ih leaded to further aggravate the damage of spatial memory. These findings indicate that dysfunctional Ih in the PV+ neuron postischemia induces the imbalance of excitation and inhibition, which might represent a novel mechanism underlying the prefrontal ischemia-induced cognitive impairment.

目的 观察关节松动术结合体外冲击波治疗卒中后踝关节挛缩的疗效.方法 选取2017年7月—2019年8月来该院就诊的30例脑卒中踝关节挛缩患者随机奇偶排列分为对照组和观察组各15例.15例奇数对照组对挛缩踝关节仅行关节松动术,15例偶数观察组踝关节在关节松动术治疗的同时在加用冲击波治疗.比较两组治疗前后踝关节被动关节活动度(PROM)及日常生活能力评分(ADL).结果 观察组和对照组治疗后踝关节被动关节活动度及日常生活能力评分较治疗前均改善,差异有统计学意义(P<0.05),观察组踝关节被动关节活动度及日常生活能力明显优于对照组,差异有统计学意义(P<0.05).结论 关节松动术结合体外冲击波治疗能够更好的改善卒中后患者踝关节挛缩程度,有效的促进患者运动功能恢复.

Objective To explore the characteristics of oligodendrocyte precursor cells in cuprizone(CPZ)-induced demyelination models.Methods Eight-week old male C57BL/6 mice were randomly divided into a control group,a demyelination group(CPZ 6 weeks) and a remyelination group(CPZ 6 weeks + normal diet 2 weeks).The mice of the control group were fed with normal diet,and those of the demyelination group and remyelination group were fed with mix diet containing 0.2% CPZ for 6 weeks.Then the mice of the remyelination group were given normal diet instead of CPZ for another 2 weeks.Luxol fast blue(LFB) staining and transmission electron microscopy were used to test the myelin sheath of corpus callosum(CC) in the brain.The expression levels of neuron-glial antigen 2(NG2),oligodendrocyte transcription factor 2(Olig2) and glial fibrillary acidic protein(GFAP) in brain tissues were detected by immunohistochemistry and immunofluorescence.Results Compared with the control group,the myelin sheath significantly reduced,and the expression levels of Olig2,GFAP and NG2 in CC were significantly higher in the demyelination group(P<0.01).The expression of NG2 in lateral septal nucleus(LSD) were higher than that in CC(P<0.05).The expression levels of Olig2 and GFAP in the remyelination group were significantly higher than that in the control group(P<0.05),but were significantly lower than that in the demyelination group(P<0.05).Conclusion Oligodendrocyte precursor cells cannot migrate to the site of injury in time.Sustained high level of astrocytes and reduction of Olig2 may be the influencing factors for myelin sheath repair disorder at the repair stage.

目的 探讨大麻素WIN55,212-2对双环己酮草酰二腙(cuprizone,CPZ)诱导C57BL/6小鼠脱髓鞘模型的治疗作用.方法 取6周龄C57BL/6雄性小鼠,分为正常组、第2周WIN55,212-2给药组与DMSO对照组、第4周WIN55,212-2给药组及DMSO对照组,每组10只.正常组每天喂养普通饲料,CPZ模型持续喂养含有0.25％ CPZ的混合饲料,在第2周和第4周时进行WIN55,212-2注射,DMSO对照组则在相同条件下注射10％的DMSO,继续喂养CPZ混合饲料.于第3、5周末通过体质量变化观察整体状态；旋转棒实验观察小鼠运动功能,利用LFB和MBP免疫组化技术染色观察胼胝体区域髓鞘,GFAP染色观察星形胶质细胞.结果 与DMSO对照组相比,WIN55,212-2给药组模型体质量下降趋势明显减缓(P＜0.05)；旋转棒实验中,WIN55,212-2给药组小鼠运动功能仍弱于正常小鼠,但是与DMSO对照组相比,WIN55,212-2给药组运动功能明显改善(P＜0.01)；LFB染色结果显示DMSO对照组髓鞘脱失明显,WIN55,212-2给药组介于正常与DMSO对照组之间,MBP染色进一步证实了这一结果；GFAP免疫组化实验结果显示DMSO对照组CPZ模型小鼠胼胝体区域GFAP阳性细胞广泛表达,而经过WIN55,212-2治疗的小鼠GFAP表达量明显低于DMSO对照组(P＜0.05).结论 大麻素WIN55,212-2可通过降低髓鞘的脱失和星形胶质细胞的活化,对脱髓鞘病变具有一定缓解的作用.