The role of Toll-like receptor 4 in apoptosis of brain tissue after induction of intracerebral hemorrhage

• Published in: Journal of neuroinflammation 2019-11, Vol.16 (1), p.234-234, Article 234
• Main Authors: Fei, Xiaowei, He, Yeting, Chen, Jia, Man, Weitao, Chen, Chen, Sun, Kai, Ding, Boyun, Wang, Chongwu, Xu, Ruxiang
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Brain; Brain - drug effects; Brain - metabolism; Cerebral Hemorrhage - genetics; Cerebral Hemorrhage - metabolism; Collagen; Collagenase; Collagenases - metabolism; Edema; Experiments; Hemorrhage; IL-1β; Inflammation; Interleukin-1beta - antagonists & inhibitors; Intracerebral hemorrhage; Kinases; Medical research; Mice; Mice, Knockout; Neurons; Polymerase chain reaction; Prognosis; Proteins; Protocol; Statistical analysis; TLR4 protein; TNF-α; Toll-like receptor 4; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor necrosis factor-α
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-019-1634-x

Inflammation and apoptosis caused by intracerebral hemorrhage (ICH) are two important factors that affect patient prognosis and survival. Toll-like receptor 4 (TLR4) triggers activation of the inflammatory pathway, causing synthesis and release of inflammatory factors. The inflammatory environment also causes neuronal apoptosis. However, no studies have reported the role of TLR4 in inflammation and apoptosis. We performed survival curve analysis and behavioral scores on TLR4 knockout mice and wild-type mice after inducing ICH. We used TLR4 knockout mice and wild-type mice to make ICH models with type VII collagenase and explored the link between TLR4 in inflammation and apoptosis. We used Western blot to detect the expression of apoptosis-related proteins, inflammatory factors, and their receptors at different time points after ICH induction. The effects of TLR4 on apoptosis were observed by TUNEL, Hoechst, and HE staining techniques. The association with TLR4 in inflammation and apoptosis was explored using IL-1β and TNF-α antagonists. Data conforming to a normal distribution are expressed as mean ± standard deviation. Grade and quantitative data were compared with rank sum test and t test between two groups. P < 0.05 was considered statistically significant. TLR4 knockout significantly increased the survival rate of ICH mice. The scores of TLR4 knockout mice were significantly lower than those of wild-type mice. We found that TLR4 knockout mice significantly inhibited apoptosis and the expression of inflammatory factors after the induction of ICH. The apoptosis of ICH-induced mice was significantly improved after injecting IL-1β and TNF-α antagonists. Moreover, the anti-apoptotic effect of the antagonist in wild-type mice is more pronounced. A single injection of the antagonist failed to improve apoptosis in TLR4 knockout mice. We conclude that TLR4-induced inflammation after ICH promotes neuronal apoptosis. IL-1β and TNF-α antagonists attenuate this apoptotic effect. Therefore, targeting TLR4 in patients with clinical ICH may attenuate inflammatory response, thereby attenuating apoptosis and improving prognosis.