Toll-like receptor-4-mediated autophagy contributes to microglial activation and inflammatory injury in mouse models of intracerebral haemorrhage

作者：Yang, Z.; Liu, B.; Zhong, L.; Shen, H.; Lin, C.; Lin, L.; Zhang, N.; Yuan, B.^*

来源：Neuropathology and Applied Neurobiology, 2015, 41(4): e95-e106.

DOI：10.1111/nan.12177

• autophagy
• ICH
• microglia
• TLR4

AimsMuch evidence demonstrates that Toll-like receptor-4 (TLR4)-mediated microglial activation is an important contributor to the inflammatory injury in intracerebral haemorrhage (ICH). However, the exact mechanism of TLR4-mediated microglial activation induced by ICH is not clear. In addition, microglial autophagy is involved other forms of nervous system injury. To explore the relationship between TLR4 and autophagy, we investigated the role of TLR4-mediated microglial autophagy and inflammation in ICH. @@@ MethodsWe detected TLR4 expression, autophagy and inflammation of microglia treated with lysed erythrocytes in vitro, and observed the cerebral water content and neurological deficit of ICH mice [TLR4-/- and wild type (WT)] in vivo. @@@ ResultsWe found that lysed erythrocyte treated microglia (TLR4-/-) had reduced autophagy and inflammation compared with microglia (WT) in vitro. ICH mice (TLR4-/-) had reduced water content and neurological injury compared with ICH mice (WT). The autophagy inhibitor (3-methyladenine) decreased microglial activation and inflammatory injury due to lysed erythrocyte treatment, and improved the neurological function of ICH mice. @@@ ConclusionsTaken together, these data suggested that TLR4 induced autophagy contributed to the microglial activation and inflammatory injury and might provide novel therapeutic interventions for ICH.

• 出版日期2015-6
• 单位浙江大学; 重庆医科大学