Nano-Curcumin Simultaneously Protects the Blood-Brain Barrier and Reduces M1 Microglial Activation During Cerebral Ischemia-Reperfusion Injury
Nano-Curcumin Simultaneously Protects the Blood-Brain Barrier and Reduces M1 Microglial Activation During Cerebral Ischemia-Reperfusion Injury
复制标题
纳米姜黄素在脑缺血再灌注损伤期间同时保护血脑屏障并减少 M1 小胶质细胞活化
DOI：
10.1021/acsami.8b20594
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发表时间：
2019-01-30
影响因子：
9.5
通讯作者：
Li, Shi-Yong
中科院分区：
文献类型：
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作者：
Wang, Ye;Luo, Jun;Li, Shi-Yong
氧化应激和炎症反应是缺血再灌注损伤后引起神经细胞凋亡和脑损伤的两个重要病理生理机制。在这里，我们假设姜黄素包裹的纳米颗粒（NP姜黄素）可以通过保护血脑屏障（BBB）和抑制M1-小胶质细胞活化来减少缺血半暗带中的氧化应激和炎症。在体外氧化应激条件下，我们发现NP姜黄素保护微血管内皮细胞免受氧化应激，并降低血脑屏障通透性。在体内，NP姜黄素可穿过血脑屏障并在缺血半暗带聚集。在I/R损伤后3d，NP姜黄素抑制MMP-9的增加，减轻occludin和noccluden-1的减少，并维持BBB的完整性。NP姜黄素有效地减少了活化的M1小胶质细胞的数量，并减弱了TNF-α和IL-β的增加。此外，NP姜黄素还减少了梗死面积，改善了功能恢复。
Oxidative stress and inflammation are two important pathophysiological mechanisms that arouse neuronal apoptosis and cerebral damage after ischemia/reperfusion (I/R) injury. Here, we hypothesized that curcumin-encapsulated nanoparticles (NPcurcumin) could reduce oxidative stress and inflammation in the ischemic penumbra via protecting the blood-brain barrier (BBB) and inhibiting M1-microglial activation. Under oxidative stress conditions in vitro, we found that NPcurcumin protected microvascular endothelial cells against oxidative stress and reduced BBB permeability. In vivo, NPcurcumin could cross the BBB and accumulate in the ischemic penumbra. At 3 d after I/R injury, NPcurcumin inhibited the increase in MMP-9, attenuated the decrease in occludin and zona occluden-1, and maintained BBB integrity. NPcurcumin effectively reduced the number of activated M1 microglia and weakened the increase in TNF-alpha and IL-beta. Furthermore, NPcurcumin also reduced the infarct size and improved function recovery.