Enhanced Therapeutic Potential of Nano-Curcumin Against Subarachnoid Hemorrhage-Induced Blood-Brain Barrier Disruption Through Inhibition of Inflammatory Response and Oxidative Stress
Enhanced Therapeutic Potential of Nano-Curcumin Against Subarachnoid Hemorrhage-Induced Blood-Brain Barrier Disruption Through Inhibition of Inflammatory Response and Oxidative Stress
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纳米姜黄素通过抑制炎症反应和氧化应激增强对蛛网膜下腔出血引起的血脑屏障破坏的治疗潜力
DOI：
10.1007/s12035-015-9635-y
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发表时间：
2017-01-01
影响因子：
5.1
通讯作者：
Sun, Bao-liang
中科院分区：
文献类型：
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作者：
Zhang, Zong-yong;Jiang, Ming;Sun, Bao-liang
姜黄素和纳米姜黄素对实验性蛛网膜下腔出血(SAH)后早期脑损伤(EBI)均有神经保护作用。然而，姜黄素及其纳米粒是否影响SAH后血脑屏障(BBB)的机制尚不清楚。本研究利用血管内穿孔大鼠SAH模型，研究姜黄素和聚丙交酯-乙交酯(PLGA)包裹的姜黄素纳米粒(CUR-NPs)对血脑屏障破坏的影响，并探讨EBI后血脑屏障功能障碍的可能机制。结果表明，在改善SAH后神经功能、降低脑含水量和伊文思蓝渗出方面，CuR-NPs的治疗效果明显优于姜黄素。从机制上讲，Cur-NPs通过阻止紧密连接蛋白(ZO-1、occludin和claudin-5)的破坏来减轻SAH后的BBB功能障碍。CUR-NPs还上调SAH后脑脊液中谷氨酸转运体-1的表达，降低谷氨酸浓度。此外，炎症反应的抑制和小胶质细胞的激活都有助于CUR-NPs的保护作用。此外，CuR-NPs显著抑制SAH介导的氧化应激，并最终逆转SAH诱导的大鼠细胞凋亡。我们的研究结果表明，使用Cur-NPs的策略可能是改善实验性大鼠蛛网膜下腔出血后EBI神经功能的一种有前途的方法。
Curcumin and nano-curcumin both exhibit neuroprotective effects in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). However, the mechanism that whether curcumin and its nanoparticles affect the blood-brain barrier (BBB) following SAH remains unclear. This study investigated the effect of curcumin and the poly(lactide-co-glycolide) (PLGA)-encapsulated curcumin nanoparticles (Cur-NPs) on BBB disruption and evaluated the possible mechanism underlying BBB dysfunction in EBI using the endovascular perforation rat SAH model. The results indicated that Cur-NPs showed enhanced therapeutic effects than that of curcumin in improving neurological function, reducing brain water content, and Evans blue dye extravasation after SAH. Mechanically, Cur-NPs attenuated BBB dysfunction after SAH by preventing the disruption of tight junction protein (ZO-1, occludin, and claudin-5). Cur-NPs also up-regulated glutamate transporter-1 and attenuated glutamate concentration of cerebrospinal fluid following SAH. Moreover, inhibition of inflammatory response and microglia activation both contributed to Cur-NPs' protective effects. Additionally, Cur-NPs markedly suppressed SAH-mediated oxidative stress and eventually reversed SAH-induced cell apoptosis in rats. Our findings revealed that the strategy of using Cur-NPs could be a promising way in improving neurological function in EBI after experimental rat SAH.