Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China.
Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China; State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, 200032, China.
Brain Res Bull. 2019 Aug;150:127-135. doi: 10.1016/j.brainresbull.2019.05.016. Epub 2019 May 24.
Interleukin-33 (IL-33) is closely related to the regulation of immunological cells, and its receptor ST2 is a member of the interleukin-1 (IL-1) receptor family. Inflammatory responses play critical roles in neuronal damage and white matter injury (WMI) post intracerebral hemorrhage (ICH). In this study, we tried to explore the role of IL-33 in neuronal damage and WMI after ICH and the underlying mechanisms. The in vivo ICH model was performed by autologous whole blood injection into the right basal ganglia in rats. Immunoblotting, immunofluorescence, brain water content measurement, FJB staining, and TUNEL staining were applied in this study. IL-33 expression was increased in whole brain tissues post-ICH, mainly rapidly increased in ipsilateral astrocyte and microglia, but stayed at a low level in neurons. Intracerebroventricular infusion of IL-33 after ICH attenuated short-term and long-term neurological deficits, WMI, neuronal degeneration, cell death and promoted the transformation of microglia phenotype from M1 to M2 in brain tissues after ICH. These results suggest that IL-33 reduces neuronal damage and WMI by promoting microglia M2 polarization after ICH, thereby improving the outcomes of neurological function.
白细胞介素-33（IL-33）与免疫细胞的调节密切相关，其受体 ST2 是白细胞介素-1（IL-1）受体家族的成员。炎症反应在脑出血（ICH）后神经元损伤和白质损伤（WMI）中起关键作用。在本研究中，我们试图探讨 IL-33 在 ICH 后神经元损伤和 WMI 中的作用及其潜在机制。通过向大鼠右侧基底核内注射自体全血来建立体内 ICH 模型。本研究应用免疫印迹、免疫荧光、脑水含量测定、FJB 染色和 TUNEL 染色。ICH 后全脑组织中 IL-33 表达增加，主要在同侧星形胶质细胞和小胶质细胞中迅速增加，但在神经元中保持低水平。ICH 后脑室内输注 IL-33 可减轻短期和长期神经功能缺损、WMI、神经元变性、细胞死亡，并促进 ICH 后脑组织中小胶质细胞表型从 M1 向 M2 的转化。这些结果表明，IL-33 通过促进 ICH 后小胶质细胞 M2 极化来减轻神经元损伤和 WMI，从而改善神经功能结局。
