Theses and Dissertations

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Browsing Theses and Dissertations by Author "Al-Shabrawey, Mohamed"

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    Traumatic Brain Injury: Assessing The Pathogenic Impact Of Chronic Smoking And Potential Countermeasures
    (2022-11-04) Sivandzade, Farzane; Cucullo, Luca; Al-Shabrawey, Mohamed; Liu Zijuan
    Traumatic brain injury is among the most prevalent causes of cerebrovascular and neurological damage worldwide. Premorbid conditions such as smoking could exacerbate post-traumatic brain injury damage and impact recovery due to vascular endothelial dysfunction. Cigarette smoke produces reactive oxygen species (ROS) and oxidative stress (OS), driving endothelial dysfunction and damaging the blood-brain barrier (BBB) endothelium. Interestingly, these pathogenic modulators of BBB impairment are similar to those initiated by hyperglycemia. Thus, this work investigated the pathophysiological mechanisms underlying traumatic brain injury (TBI) exacerbation following chronic smoking and vaping exposure to determine key pathological parameters leading to loss of BBB function and integrity. I also assessed the effectiveness of metformin and rosiglitazone to prevent/reduce the loss of BBB function and integrity and protect the brain from the exacerbation of post-TBI likely promoted by the chronic exposure to tobacco smoke (TS) or electronic cigarette (EC) vape and unravel the corresponding mechanism (s) of action. For this purpose, I used both in vitro (primary brain microvascular endothelial cells) and in vivo mice models (male and C57BL/6J mice) subjected to TS/EC and TBI, with/without antidiabetic treatments. The outcomes of these studies would define the complex interplay between smoking and TBI and lead to new approaches for alleviating TBI outcomes.