Necrostatin-1 decreases necroptosis and inflammatory markers after intraventricular hemorrhage in mice

坏死抑制素-1 降低小鼠脑室内出血后的坏死凋亡和炎症标志物

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作者:Chang Liu, Yi Cao, Hao-Xiang Wang, Long Zhao, Ya-Xing Chen, Kun-Hong Zhong, Gao-Wei Li, Guo-Qing Wang, Ke-Ru Huang, Ai-Ping Tong, Liang-Xue Zhou

Abstract

Necrostatin-1, an inhibitor of necroptosis, can effectively inhibit necrotic apoptosis in neurological diseases, which results in the inhibition of inflammation, endoplasmic reticulum stress, and reactive oxygen species production and substantial improvement of neurological function. However, the effects of necrostatin-1 on intraventricular hemorrhage (IVH) remain unknown. In this study, we established a mouse model of IVH by injecting autologous blood into the lateral ventricle of the brain. We also injected necrostatin-1 into the lateral ventricle one hour prior to IVH induction. We found that necrostatin-1 effectively reduced the expression levels of the necroptosis markers receptor-interacting protein kinase (RIP)1, RIP3, mixed lineage kinase domain-like protein (MLKL), phosphorylated (p)-RIP3, and p-MLKL and the levels of interleukin-1β , interleukin-6, and tumor necrosis factor-α in the surrounding areas of the lateral ventricle. However, necrostatin-1 did not reduce ependymal ciliary injury or brain water content. These findings suggest that necrostatin-1 can prevent local inflammation and microglial activation induced by IVH but does not greatly improve prognosis.

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