Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University.
Department of Ultrasound.
Neuroreport. 2021 Oct 6;32(14):1161-1169. doi: 10.1097/WNR.0000000000001704.
After ischemic stroke, microglia will be activated and play a key role in neuroinflammation and the destruction of the blood-brain barrier (BBB), and activated microglia could polarize into pro-inflammation M1 phenotype and anti-inflammation M2 phenotype. Dimethyl malonate (DMM) could reduce reactive oxygen species and we speculate DMM could regulate microglia to protect ischemic brain.
We used transient middle cerebral artery occlusion (tMCAO) mouse model to simulate ischemic stroke and adult male C57BL/6 mice were used in our study. 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct volume. Evans Blue and Brain water content were used to evaluate the destruction of BBB. We used a five-point scale to assess the neurologic function of mice. Western blot and Immunofluorescence were used to measure microglia, pericytes and the expression of related proteins.
DMM reduced cerebral infarct volume, Evans blue leakage, brain water content and improved neurologic deficits after tMCAO. The number of activated microglia and M1 microglia were decreased and the number of M2 microglia and pericytes were increased after DMM treatment. The expression of tumor necrosis factor-α was reduced while protein levels of IL-10 and ZO-1 were increased through DMM treatment.
DMM could regulate activation and polarization of microglia to inhibit neuroinflammation and protect BBB.
脑缺血后，小胶质细胞被激活，并在神经炎症和血脑屏障（BBB）破坏中发挥关键作用，激活的小胶质细胞可极化为促炎 M1 表型和抗炎 M2 表型。丙二酰基二甲酯（DMM）可减少活性氧，我们推测 DMM 可调节小胶质细胞以保护缺血性大脑。
我们使用短暂性大脑中动脉闭塞（tMCAO）小鼠模型模拟缺血性中风，研究使用成年雄性 C57BL/6 小鼠。2,3,5-三苯基氯化四氮唑染色用于测量梗死体积。伊文思蓝和脑水含量用于评估 BBB 的破坏。我们使用五分制评估小鼠的神经功能。Western blot 和免疫荧光用于测量小胶质细胞、周细胞和相关蛋白的表达。
DMM 可减少 tMCAO 后的脑梗死体积、伊文思蓝漏出、脑水含量和改善神经功能缺损。DMM 治疗后，激活的小胶质细胞和 M1 小胶质细胞的数量减少，M2 小胶质细胞和周细胞的数量增加。通过 DMM 治疗，肿瘤坏死因子-α的表达减少，IL-10 和 ZO-1 的蛋白水平增加。
DMM 可调节小胶质细胞的激活和极化，抑制神经炎症并保护 BBB。
