Microglia play a key role in the immune response and inflammatory reaction that occurs in response to ischemic stroke. Activated microglia promote neuronal damage or protection in injured brain tissue. Extracellular signals polarize the microglia towards the M1/M2 phenotype. The M1/M2 phenotype microglia released pro- and anti-inflammatory cytokines which induce the activation of neural stem/progenitor cells (NSPCs). In this study, we investigated how the cytokines released by microglia affect the activation of NSPCs. First, we treated BV2 cells with a lipopolysaccharide (LPS; 20 ng/ml) for M1 phenotype microglia and interleukin-4 (IL-4; 20 ng/ml) for M2 phenotype microglia in BV2 cells. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 1 h. In ex vivo, brain sections containing the subventricular zone (SVZ) were cultured in conditioned media of M1 and M2 phenotype-conditioned media for 3 d. We measured the expression of cytokines in the conditioned media by RT-PCR and ELISA. The M2 phenotype microglia-conditioned media led to the proliferation and neural differentiation of NSPCs in the ipsilateral SVZ after ischemic stroke. The RT-PCR and ELISA results showed that the expression of TGF-α mRNA was significantly higher in the M2 phenotype microglia-conditioned media. These data support that M2 phenotype microglia-derived TGF-α is one of the key factors to enhance proliferation and neural differntiation of NSPCs after ischemic stroke.

中文翻译：

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M2表型小胶质细胞源性细胞因子刺激缺血性脑内源性干细胞的增殖和神经元分化。

小胶质细胞在针对缺血性中风的免疫反应和炎症反应中起关键作用。活化的小胶质细胞促进受伤的脑组织中的神经元损伤或保护。细胞外信号使小胶质细胞向M1 / M2表型极化。M1 / M2表型小胶质细胞释放促炎和抗炎细胞因子，从而诱导神经干/祖细胞（NSPC）的激活。在这项研究中，我们调查了小胶质细胞释放的细胞因子如何影响NSPC的激活。首先，我们用脂多糖（LPS; 20 ng / ml）处理BV2细胞以治疗M1表型小胶质细胞，使用白细胞介素4（IL-4; 20 ng / ml）治疗BV2细胞中的M2表型小胶质细胞。小鼠经历短暂的大脑中动脉闭塞（tMCAO）1小时。在体外，在M1和M2表型条件培养液中培养含有脑室下区（SVZ）的大脑切片3 d。我们通过RT-PCR和ELISA测定了条件培养基中细胞因子的表达。M2表型小胶质细胞条件培养基导致缺血性中风后同侧SVZ中NSPC的增殖和神经分化。RT-PCR和ELISA结果表明，在M2表型小胶质细胞条件培养基中，TGF-αmRNA的表达明显较高。这些数据支持M2型小胶质细胞衍生的TGF-α是增强缺血性中风后NSPCs增殖和神经分化的关键因素之一。