Tim-3 deteriorates neuroinflammatory and neurocyte apoptosis after subarachnoid hemorrhage through the Nrf2/HMGB1 signaling pathway in rats.

Tim-3 deteriorates neuroinflammatory and neurocyte apoptosis after subarachnoid hemorrhage through the Nrf2/HMGB1 signaling pathway in rats. Aging (Albany NY). 2020 Nov 07;12: Authors: Guo S, Li Y, Wei B, Liu W, Li R, Cheng W, Zhang X, He X, Li X, Duan C Abstract Inflammation is known to play an important role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). T cell immunoglobulin and mucin domain-3 (Tim-3) has emerged as a critical regulator of adaptive and innate immune responses, and has been identified to play a vital role in certain inflammatory diseases; The present study explored the effect of Tim-3 on inflammatory responses and detailed mechanism in EBI following SAH. We investigated the effects of Tim-3 on SAH models established by endovascular puncture method in Sprague-Dawley rats. The present studies revealed that SAH induced a significant inflammatory response and significantly increased Tim-3 expression. Tim-3-AAV administration aggravated neurocyte apoptosis, brain edema, blood-brain barrier permeability, and neurological dysfunction; significantly inhibited Nrf2 expression; and increased HMGB1 expression and secretion of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin (IL)-1 beta, IL-17, and IL-18. However, Tim-3 siRNA or NK252 administration abolished the pro-inflammatory effects of Tim-3. Our results indicate a function for Tim-3 as a molecular player that links neuroinfla...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research