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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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Abstract

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.

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Acknowledgments

The national natural science foundation of China (NSFC) (nos.81301018, 81501106, and 81271275) and the China Postdoctoral Science Foundation Grant (2014 M560355) supported this work.

Contributors

ZZ, CF, and BS conceived the project and designed experiments. ZZ, MJ, JF, MY, ZS, YY, DL, FX, WK, HY, and LM performed the experiments; CF and BS analyzed the results. ZZ and CF wrote the manuscript. All authors read and approved the final manuscript.

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    Authors and Affiliations

    1. Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China

      Zong-yong Zhang, Jie Fang, Ming-feng Yang, Shuai Zhang, Da-wei Li, Lei-lei Mao, Xiao-yan Fu, Ya-jun Hou, Xiao-ting Fu, Cun-dong Fan & Bao-liang Sun

    2. Biomedical Research Center of Tongji University Suzhou Institute, 215101, Suzhou, Jiangsu, China

      Ming Jiang & Yan-xin Yin

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    Zong-yong Zhang, Ming Jiang and Jie Fang contributed equally to this work.

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    Zhang, Zy., Jiang, M., Fang, J. et al. Enhanced Therapeutic Potential of Nano-Curcumin Against Subarachnoid Hemorrhage-Induced Blood–Brain Barrier Disruption Through Inhibition of Inflammatory Response and Oxidative Stress. Mol Neurobiol 54, 1–14 (2017). https://doi.org/10.1007/s12035-015-9635-y

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