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

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 neuroinflammation and brain damage after SAH. We reveal that TIM-3 overexpression deteriorates neuroinflammatory and neurocyte Apoptosis after subarachnoid hemorrhage through the Nrf2/HMGB1 signaling pathway in rats.