期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 25, 期 15, 页码 7122-7134出版社
WILEY
DOI: 10.1111/jcmm.16741
关键词
alternative; blood-brain barrier; endothelium; in vitro; inflammation; Nrf2; oxidative stress; smoking; TBI; traumatic injury
资金
- National Institutes of Health/National Institute on Drug Abuse [2R01--DA029121, 1R01-DA049737]
- National Institute of Neurological Disorders and Stroke [1R01-NS117906]
Chronic tobacco smoking exacerbates traumatic endothelial injury, reduces BBB endothelial cell viability, increases oxidative stress and inflammation, and potentially leads to severe neurological impairments.
Traumatic brain injury (TBI) is a major reason of cerebrovascular and neurological damage. Premorbid conditions such as tobacco smoking (TS) can worsen post-TBI injuries by promoting vascular endothelial impairments. Indeed, TS-induced oxidative stress (OS) and inflammation can hamper the blood-brain barrier (BBB) endothelium. This study evaluated the subsequence of chronic TS exposure on BBB endothelial cells in an established in vitro model of traumatic cell injury. Experiments were conducted on confluent TS-exposed mouse brain microvascular endothelial cells (mBMEC-P5) following scratch injury. The expression of BBB integrity-associated tight junction (TJ) proteins was assessed by immunofluorescence imaging (IF), Western blotting (WB) and quantitative RT-PCR. We evaluated reactive oxygen species (ROS) generation, the nuclear factor 2-related (Nrf2) with its downstream effectors and several inflammatory markers. Thrombomodulin expression was used to assess the endothelial haemostatic response to injury and TS exposure. Our results show that TS significantly decreased Nrf2, thrombomodulin and TJ expression in the BBB endothelium injury models while increased OS and inflammation compared to parallel TS-free cultures. These data suggest that chronic TS exposure exacerbates traumatic endothelial injury and abrogates the protective antioxidative cell responses. The downstream effect was a more significant decline of BBB endothelial viability, which could aggravate subsequent neurological impairments.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据