Neuroinflammation, defined as an inflammatory response mediated by central nervous system astrocyte, Microglia and endothelial cells, disrupts homeostasis and is typical of many Neurodegeneration. The DA receptor family is mainly expressed in Microglia, and microglia-induced neuroinflammation is an important pathogenesis of Neurodegeneration, this article reviews the pathogenesis and treatment of neuroinflammation.

Objective:To investigate the effect of paired associative stimulation (PAS) on the recovery of neurological function after cerebral infarction, and to explore whether any such effect is associated with autophagy in the ischemic penumbra.Methods:Sixty adult male Sprague-Dawley rats were randomly divided into a sham operation group ( n=20) and an experimental group ( n=40). The rats of the experimental group underwent 90 minutes of right middle cerebral artery occlusion (MCAO), while the sham group received a sham operation. The experimental group was subsequently divided into a model group ( n=20) and a PAS group ( n=20). The PAS group received 14 days of paired associative stimulation (PAS) beginning 24 hours after the operation. Neurological dysfunction was evaluated with a modified neurological severity scale (mNSS) and the elevated body swing test (EBST) on the 1st, 7th and 14th day after the MCAO. The rats were then euthanized and the expression of LC3Ⅰ, LC3Ⅱ, Beclin1, and Cathepsin B in the ischemic penumbra were detected using Western blotting, while the distribution of LC3 in neurons was detected using double immunofluorescent staining. Results:Compared with the sham group, the average mNSS scores and EBST values of the model and PAS groups were both higher on the 7th and 14th day after the MCAO, with those of the PAS group significantly lower than those of the model group on those days. The average mNSS score on the 14th day was significantly lower than on the 7th day. Compared with the sham group, the average LC3Ⅱ/Ⅰ values, Beclin 1 and Cathepsin B levels of both the model group and the PAS group were significantly higher on the 7th and 14th day after the MCAO, with the LC3Ⅱ/Ⅰ values of the PAS group significantly lower than those of the model group at both time points. The PAS group also had significantly lower Beclin1 and Cathepsin B levels on day 14. On the 7th and 14th days after the MCAO, the average number of LC3-positive cells and the ratio of LC3-positive neurons to total neurons in the model and PAS groups were significantly greater than the those of sham group, with the PAS group′s values significantly lower than those of the model group at each time point.Conclusion:PAS can significantly promote neurological recovery after stroke. The beneficial effects may involve inhibition of neuronal autophagy in the ischemic penumbra.

目的:观察成对关联刺激对缺血性脑卒中大鼠缺血半暗带区NogoA、NgR、RhoA蛋白表达的影响.方法:90只健康雄性SD大鼠随机分为假手术组、模型组和PAS组,每组又分为7d、14d、28d三个亚组(n=10).模型组和PAS组大鼠采用Longa线栓法制作MCAO模型,假手术组除不插入线栓外,其余操作与模型组和PAS组相同.PAS组于术后第1d开始给予0.05Hz、共90对脉冲的PAS治疗,每日1次,每次持续30min;模型组和假手术组不予任何干预措施,各时间点治疗结束后取缺血半暗带区脑组织,Western Blot和免疫荧光检测缺血半暗带NogoA、NgR、RhoA蛋白的表达和分布情况.结果:术后第7、14、28d,假手术组NogoA、NgR、RhoA蛋白的表达水平均最低,模型组在各时间点NogoA、NgR、RhoA含量均较假手术组明显升高(P＜0.05),PAS组术后各时间点NogoA、NgR、RhoA的含量高于假手术组(P＜0.05),低于同时间点模型组(P＜0.05),PAS组NogoA、NgR、RhoA蛋白在术后28d的含量低于同组第7d、14d(P＜0.05).结论:PAS可抑制NogoA/NgR/RhoA信号通路蛋白的表达,可能是PAS促进脑缺血大鼠神经再生,改善脑缺血大鼠的感觉运动功能障碍的内在分子机制之一.

Objective To observe the effects of paired associative stimulation ( PAS) on synaptic ultrastruc-ture, neuron apoptosis and BDNF in rats with cerebral infarct, and explore the possible underlying mechanisms. Methods Forty-five male Sprague-Dawley rats were randomly divided into three groups:a sham operation group, a model group and a PAS group, with 15 rats in each. All the rats underwent a surgical operation for transient middle cerebral artery occlusion ( MCAO) on the right side to model focal cerebral ischemia, with those in the sham opera-tion group left without real occlusion. PAS treatment was given to rats in the PAS group 24h after MCAO model was successfully established, while no special intervention was given to those in the sham operation group and model group. After 28 days of treatment, transmission electron microscopy was used to investigate the ultrastructure of the is-chemic penumbra, TUNEL was used to observe the apoptosis of cortex neurons, and real time-PCR to investigate BDNF mRNA expression. Results It was found that after 28 days treatment:①The synaptic curvature, the synapse length and the post-synaptic density ( PSD) decreased significantly in the rats of model group in contrast to those of the sham control group ( P<0.05) . And compare to model group, the synaptic curvature, the synapse length and the PSD increased significantly in the rats of PAS group ( P<0.05) . ②Compare to sham control group, the apoptosis rate of model group and PAS group increased significantly ( P<0.05) . And the apoptosis rate of PAS group decreased sig-nificantly in contrast to those of model group ( P<0.05) .③Compare to sham control group, BDNF mRNA expression of the PAS group increased significantly( P<0.05) , while BDNF mRNA expression of the model group decreased sig-nificantly( P<0.05) . BDNF mRNA expression of the PAS group increased significantly in contrast to those of model group ( P<0.05) . Conclusion PAS promotes neural plasticity and inhibits apoptosis of cortex neurons of the ische-mic penumbra in rats with ischemic cerebral infarction. One of the underlying mechanisms might be related to the up-regulation of BDNF mRNA expression.

Objective To observe the effect of paired associative stimulation ( PAS) on the recovery of sensorimotor function and to explore the mechanism in terms of neural plasticity. Methods Ninety male adult Sprague-Dawley rats were randomly divided into a sham operation group (Sham group), a model group (Model group) and a paired associative stimulation group ( PAS group) , each of 30. Each group was then subdivided into 7-, 14-and 28-day subgroups with 10 rats in each. A model of focal cerebral ischemia and reperfusion was estab-lished using the Longa suture method in the Model and PAS groups. The rats in the Sham group underwent the same surgical procedure except for the occlusion of the middle cerebral artery. The rats received 30 minutes of paired pe-ripheral nerve stimulation and transcranial magnetic stimulation comprising 90 pairs at 0.05 Hz beginning 24 h after the occlusion. The impulse wave width of the peripheral nerve stimulation was 200 μs and the intensity was 6 mA. The intensity of the transcranial magnetic stimulation was 120％ of the resting motor threshold. The other two groups weren't given any intervention. Neurological function was tested using Garcia scores on the 1st, 7th, 14th and 28th day after surgery. The rats were then sacrificed and the expression of MAP-2 and GAP-43 in the ischemic penumbra were detected using western blotting and immunohistochemistry. Results No neurological dysfunction was ob-served in the Sham group at any time. Compared with the Sham group at the same time points, the average Garcia scores of the Model and PAS groups were significantly lower (P≤0.05). However, the average Garcia scores on the 7th, 14th and 28th day were significantly higher in the PAS group compared with the Model group at the same time points ( P≤0.05) . The average Garcia scores of the Model and PAS groups on the 28th day after surgery were significantly higher than those on the 1st day (P≤0.05), but only the PAS group's average Garcia score on the 28th day was significantly higher than that on the 7th day. Compared with the Sham group at the same time points, the expression of MAP-2 and GAP-43 protein in the Model and PAS groups was significantly higher, but with that of the Model group significantly lower than that of the PAS group ( all P≤0.05) . The protein expression of MAP-2 and GAP-43 protein in the PAS group on the 14th day was significantly higher than on the 7th and 28th day ( P≤0.05 for both) . Conclusions PAS can promote the recovery of sensorimotor function after cerebral thrombosis, at least in rats. That may be due to its promoting the expression of the neuroplasticity-associated proteins MAP-2 and GAP-43 in the ischemic penumbra.