Guo Yan, Zhang Xiangyu, Deng Jianzhong, Su Qiuyang, Liu Yuanyuan, Yan Gaili, Xue Sara, Yong V Wee, Xue Mengzhou
Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China; Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan, 450000, China; Department of Neurology, Anyang District Hospital of Henan Province, Anyang, Henan, 455000, China.
Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China; Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan, 450000, China.
Neuropharmacology. 2025 Nov 1;278:110538. doi: 10.1016/j.neuropharm.2025.110538. Epub 2025 May 29.
Intracerebral hemorrhage (ICH) accounts for 10-15 % of all stroke cases and is associated with high mortality and morbidity. Brain injury caused by ICH includes primary and secondary brain injury. Neuroinflammation and apoptosis play important roles in the pathological process of secondary brain injury after ICH. Urolithin A (UroA) is a metabolite derived from ellagic acid and has been confirmed to be anti-inflammatory, anti-oxidant and anti-apoptotic. The aim of this study was to investigate the effects of UroA on neuroinflammation and neuronal apoptosis in a mouse model of ICH induced by collagenase. Compared with ICH mice given vehicle, intraperitoneal injection of UroA (2.5 mg/kg) significantly reduced neurological impairment and brain water content 3 days after ICH. UroA reduced Evans Blue exudation and the loss of zonula occludens-1 and Occludin. Western blot showed that UroA significantly decreased the concentration of matrix metalloproteinases-9 (MMP-9). UroA treatment significantly attenuated the density of activated microglia and infiltrated neutrophils after 3 days of ICH. Finally, UroA inhibited cell death around the hematoma, attenuated ipsilateral brain injury, and improved neurological function in mice with ICH. UroA plays a neuroprotective role in ICH by inhibiting the expression of MMP-9 and reducing neuroinflammation, blood-brain barrier destruction, brain cell death and brain injury.
脑出血（ICH）占所有中风病例的10 - 15%，并与高死亡率和高发病率相关。ICH所致脑损伤包括原发性和继发性脑损伤。神经炎症和细胞凋亡在ICH后继发性脑损伤的病理过程中起重要作用。尿石素A（UroA）是一种源自鞣花酸的代谢产物，已被证实具有抗炎、抗氧化和抗凋亡作用。本研究旨在探讨UroA对胶原酶诱导的ICH小鼠模型中神经炎症和神经元凋亡的影响。与给予赋形剂的ICH小鼠相比，腹腔注射UroA（2.5 mg/kg）显著降低了ICH后3天的神经功能缺损和脑含水量。UroA减少了伊文思蓝渗出以及紧密连接蛋白-1和闭合蛋白的丢失。蛋白质印迹法显示UroA显著降低了基质金属蛋白酶-9（MMP-9）的浓度。UroA治疗显著减轻了ICH 3天后活化小胶质细胞和浸润中性粒细胞的密度。最后，UroA抑制了血肿周围的细胞死亡，减轻了同侧脑损伤，并改善了ICH小鼠的神经功能。UroA通过抑制MMP-9的表达并减少神经炎症、血脑屏障破坏、脑细胞死亡和脑损伤，在ICH中发挥神经保护作用。
