Zhao Yang1, B Liu1, L Zhong1, Hanchao Shen2, Chuangan Lin2, Li Lin2, Nan Zhang3, Bangqing Yuan2. 1. Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing. 2. Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian. 3. Department of Urology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract
AIMS: Much 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: Taken together, these data suggested that TLR4 induced autophagy contributed to the microglial activation and inflammatory injury and might provide novel therapeutic interventions for ICH.
AIMS: Much 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. METHODS: We detected TLR4 expression, autophagy and inflammation of microglia treated with lysed erythrocytes in vitro, and observed the cerebral water content and neurological deficit of ICHmice [TLR4-/- and wild type (WT)] in vivo. RESULTS: We found that lysed erythrocyte treated microglia (TLR4-/-) had reduced autophagy and inflammation compared with microglia (WT) in vitro. ICHmice (TLR4-/-) had reduced water content and neurological injury compared with ICHmice (WT). The autophagy inhibitor (3-methyladenine) decreased microglial activation and inflammatory injury due to lysed erythrocyte treatment, and improved the neurological function of ICHmice. CONCLUSIONS: Taken together, these data suggested that TLR4 induced autophagy contributed to the microglial activation and inflammatory injury and might provide novel therapeutic interventions for ICH.
Authors: Marietta Zille; Saravanan S Karuppagounder; Yingxin Chen; Peter J Gough; John Bertin; Joshua Finger; Teresa A Milner; Elizabeth A Jonas; Rajiv R Ratan Journal: Stroke Date: 2017-03-01 Impact factor: 7.914