Urolithin A alleviates blood-brain barrier disruption and attenuates neuronal apoptosis following traumatic brain injury in mice  

作　　者：Qiu-Yuan Gong Lin Cai Yao Jing Wei Wang Dian-Xu Yang Shi-Wen Chen Heng-Li Tian 

机构地区：[1]Department of Neurosurgery,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,Shanghai,China

出　　处：《Neural Regeneration Research》2022年第9期2007-2013,共7页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.81974189(to HLT),81801236(to QYG and LC),82001310(to DXY).

摘　　要：Urolithin A(UA)is a natural metabolite produced from polyphenolics in foods such as pomegranates,berries,and nuts.UA is neuroprotective against Parkinson’s disease,Alzheimer’s disease,and cerebral hemorrhage.However,its effect against traumatic brain injury remains unknown.In this study,we established adult C57BL/6J mouse models of traumatic brain injury by controlled cortical impact and then intraperitoneally administered UA.We found that UA greatly reduced brain edema;increased the expression of tight junction proteins in injured cortex;increased the immunopositivity of two neuronal autophagy markers,microtubule-associated protein 1A/B light chain 3A/B(LC3)and p62;downregulated protein kinase B(Akt)and mammalian target of rapamycin(mTOR),two regulators of the phosphatidylinositol 3-kinase(PI3K)/Akt/mTOR signaling pathway;decreased the phosphorylation levels of inhibitor of NFκB(IκB)kinase alpha(IKKα)and nuclear factor kappa B(NFκB),two regulators of the neuroinflammation-related Akt/IKK/NFκB signaling pathway;reduced blood-brain barrier permeability and neuronal apoptosis in injured cortex;and improved mouse neurological function.These findings suggest that UA may be a candidate drug for the treatment of traumatic brain injury,and its neuroprotective effects may be mediated by inhibition of the PI3K/Akt/mTOR and Akt/IKK/NFκB signaling pathways,thus reducing neuroinflammation and enhancing autophagy.

关 键 词：AUTOPHAGY blood-brain barrier cerebral edema controlled cortical impact model neuronal apoptosis NEUROPHARMACOLOGY NEUROPROTECTION tight junction protein traumatic brain injury urolithin A 

分 类 号：R651.15[医药卫生—外科学]