Yuan Jichao, Liu Wei, Zhu Haitao, Zhang Xuan, Feng Yang, Chen Yaxing, Feng Hua, Lin Jiangkai
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
J Surg Res. 2017 Jan;207:85-91. doi: 10.1016/j.jss.2016.08.090. Epub 2016 Sep 3.
Early brain injury, one of the most important mechanisms underlying subarachnoid hemorrhage (SAH), comprises edema formation and blood-brain barrier (BBB) disruption. Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unknown neuroprotective mechanisms. In this study, we examined whether curcumin treatment ameliorates SAH-induced brain edema and BBB permeability changes, as well as the mechanisms underlying this phenomenon.
We induced SAH in mice via endovascular perforation, administered curcumin 15 min after surgery and evaluated neurologic scores, brain water content, Evans blue extravasation, Western blot assay results, and immunohistochemical analysis results 24 h after surgery.
Curcumin significantly improved neurologic scores and reduced brain water content in treated mice compared with SAH mice. Furthermore, curcumin decreased Evans blue extravasation, matrix metallopeptidase-9 expression, and the number of Iba-1-positive microglia in treated mice compared with SAH mice. At last, curcumin treatment increased the expression of the tight junction proteins zonula occludens-1 and occludin in treated mice compared with vehicle-treated and sample SAH mice.
We demonstrated that curcumin inhibits microglial activation and matrix metallopeptidase-9 expression, thereby reducing brain edema and attenuating post-SAH BBB disruption in mice.
早期脑损伤是蛛网膜下腔出血(SAH)最重要的发病机制之一,包括水肿形成和血脑屏障(BBB)破坏。姜黄素是姜黄根茎的一种活性提取物,通过尚不明确的神经保护机制减轻神经炎症。在本研究中,我们检测了姜黄素治疗是否能改善SAH诱导的脑水肿和BBB通透性变化,以及这一现象背后的机制。
我们通过血管内穿刺在小鼠中诱导SAH,术后15分钟给予姜黄素,并在术后24小时评估神经功能评分、脑含水量、伊文思蓝外渗、蛋白质免疫印迹分析结果和免疫组织化学分析结果。
与SAH小鼠相比,姜黄素显著改善了治疗小鼠的神经功能评分并降低了脑含水量。此外,与SAH小鼠相比,姜黄素减少了治疗小鼠的伊文思蓝外渗、基质金属蛋白酶-9表达和Iba-1阳性小胶质细胞数量。最后,与载体处理和样本SAH小鼠相比,姜黄素治疗增加了治疗小鼠中紧密连接蛋白闭合蛋白-1和闭合蛋白的表达。
我们证明姜黄素抑制小胶质细胞活化和基质金属蛋白酶-9表达,从而减轻小鼠脑水肿并减轻SAH后BBB破坏。