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Dl-3n-butylphthalide improves traumatic brain injury recovery via inhibiting autophagy-induced blood-brain barrier disruption and cell apoptosis.


ABSTRACT: Blood-brain barrier (BBB) disruption and neuronal apoptosis are important pathophysiological processes after traumatic brain injury (TBI). In clinical stroke, Dl-3n-butylphthalide (Dl-NBP) has a neuroprotective effect with anti-inflammatory, anti-oxidative, anti-apoptotic and mitochondrion-protective functions. However, the effect and molecular mechanism of Dl-NBP for TBI need to be further investigated. Here, we had used an animal model of TBI and SH-SY5Y/human brain microvascular endothelial cells to explore it. We found that Dl-NBP administration exerts a neuroprotective effect in TBI/OGD and BBB disorder, which up-regulates the expression of tight junction proteins and promotes neuronal survival via inhibiting mitochondrial apoptosis. The expressions of autophagy-related proteins, including ATG7, Beclin1 and LC3II, were significantly increased after TBI/OGD, and which were reversed by Dl-NBP treatment both in vivo and in vitro. Moreover, rapamycin treatment had abolished the effect of Dl-NBP for TBI recovery. Collectively, our current studies indicate that Dl-NBP treatment improved locomotor functional recovery after TBI by inhibiting the activation of autophagy and consequently blocking the junction protein loss and neuronal apoptosis. Dl-NBP, as an anti-inflammatory and anti-oxidative drug, may act as an effective strategy for TBI recovery.

SUBMITTER: Wu F 

PROVIDER: S-EPMC6991645 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Dl-3n-butylphthalide improves traumatic brain injury recovery via inhibiting autophagy-induced blood-brain barrier disruption and cell apoptosis.

Wu Fangfang F   Xu Ke K   Xu Kebin K   Teng Chenhuai C   Zhang Man M   Xia Leilei L   Zhang Kairui K   Liu Lei L   Chen Zaifeng Z   Xiao Jian J   Wu Yanqing Y   Zhang Hongyu H   Chen Daqing D  

Journal of cellular and molecular medicine 20191216 2


Blood-brain barrier (BBB) disruption and neuronal apoptosis are important pathophysiological processes after traumatic brain injury (TBI). In clinical stroke, Dl-3n-butylphthalide (Dl-NBP) has a neuroprotective effect with anti-inflammatory, anti-oxidative, anti-apoptotic and mitochondrion-protective functions. However, the effect and molecular mechanism of Dl-NBP for TBI need to be further investigated. Here, we had used an animal model of TBI and SH-SY5Y/human brain microvascular endothelial c  ...[more]

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