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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 …