Neuroinflammation contributes to neuronal death in cerebral ischemia. Urolithin A (UA), a gut microbial metabolite of ellagic acid, has emerged as a potential anti-inflammatory agent. However, its roles and precise mechanisms in stroke remain unknown. Here we found that UA treatment ameliorated infarction, neurological deficit scores, and spatial memory deficits after cerebral ischemia. Furthermore, UA significantly reduced neuron loss and promoted neurogenesis after ischemic stroke. We also found that UA attenuated apoptosis by regulating apoptotic-related proteins. Meanwhile, UA treatment inhibited glial activation via affecting inflammatory signaling pathways, specifically by enhancing cerebral AMPK and IκBa activation while decreasing the activation of Akt, P65NFκB, ERK, JNK, and P38MAPK. Our findings reveal a key role of UA against ischemic stroke through modulating apoptosis and neuroinflammation in mice.

神经炎症导致脑缺血中神经元死亡。鞣花酸的肠道微生物代谢产物尿石素A（UA）已成为一种潜在的抗炎药。然而，其在中风中的作用和精确机制仍然未知。在这里，我们发现UA治疗可改善脑缺血后的梗塞，神经功能缺损评分和空间记忆障碍。此外，UA可显着减少缺血性中风后神经元的丢失并促进神经发生。我们还发现UA通过调节凋亡相关蛋白来减弱细胞凋亡。同时，UA治疗通过影响炎症信号通路抑制神经胶质细胞的活化，特别是通过增强脑AMPK和IκBa的活化，同时降低Akt，P65NFκB，ERK，JNK和P38MAPK的活化来抑制神经胶质的活化。