神经炎症
创伤性脑损伤
背景(考古学)
小胶质细胞
促炎细胞因子
炎症
神经科学
信号转导
医学
生物
免疫学
细胞生物学
精神科
古生物学
作者
Xiupeng Xu,Tongle Zhi,Lingyang Hua,Kuan Jiang,Chen Chen
标识
DOI:10.1016/j.expneurol.2022.114007
摘要
Although multiple signaling pathways contributing to the pathophysiological process have been investigated, treatments for traumatic brain injury (TBI) against present targets have not acquired significant clinical progress. Interleukin-1 receptor-associated kinase 4 (IRAK4) is an important factor involved in regulating immunity and inflammation. However, the role of IRAK4 in TBI still remains largely unknown. Therefore, using a controlled cortical impact model (CCI), we investigated the function and molecular mechanism of IRAK4 in the context of TBI. IRAK4 was found to be activated in a time-dependent manner after TBI and mainly expressed in neurons. Inhibition of IRAK4 by siRNAs could significantly alleviates neuroinflammation, neuron apoptosis, brain edema, brain-blood barrier (BBB) dysfunction and improves neurological deficit in the context of CCI. Mechanistically, IRAK4 exacerbates CCI via activation of TAK1 signaling pathway. Interestingly, PF-0665083, an IRAK4 inhibitor, inhibits phosphorylation of IRAK4 and attenuates CCI-induced secondary injury. It could be conclude that IRAK4 plays a critical role in TBI-induced secondary injury and the underlining mechanism may be related to activation of TAK1 signaling pathway. PF-0665083 may serve as a potential treatment strategy to relieve TBI.
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