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Published in: Journal of Neuroinflammation 1/2020

01-12-2020 | Central Nervous System Trauma | Research

The cerebrovascular and neurological impact of chronic smoking on post-traumatic brain injury outcome and recovery: an in vivo study

Authors: Farzane Sivandzade, Faleh Alqahtani, Ali Sifat, Luca Cucullo

Published in: Journal of Neuroinflammation | Issue 1/2020

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Abstract

Background

Traumatic brain injury (TBI) is among the most prevalent causes of cerebrovascular and neurological damage worldwide. To this end, tobacco smoke (TS) has been shown to promote vascular inflammation, neurovascular impairments, and risk of cerebrovascular and neurological disorders through oxidative stress (OS) stimuli targeting the blood-brain barrier (BBB) endothelium among others. It has been recently suggested that premorbid conditions such as TS may exacerbate post-TBI brain damage and impact recovery.

Methods

Our study investigated the mechanisms underlying the exacerbation of TBI injury by TS using a weight drop model. For this purpose, male C57BL/6J mice, age range 6–8 weeks, were chronically exposed to premorbid TS for 3 weeks. Test animals were then subjected to TBI by guided vertical head weight drop using a 30 g metal weight free felling from an 80 cm distance before reaching the target. We analyzed the physical activity and body weight of the mice before TBI and 1 h, 24 h, and 72 h post-injury. Finally, mice were sacrificed to collect blood and brain samples for subsequent biochemical and molecular analysis. Western blotting was applied to assess the expression of Nrf2 (a critical antioxidant transcription factor) as well as tight junction proteins associated with BBB integrity including ZO-1, Occludin, and Claudin-5 from brain tissues homogenates. Levels of NF-kB (a pro-inflammatory transcript factor which antagonizes Nrf2 activity) and pro-inflammatory cytokines IL-6, IL-10, and TNF-α were assessed in blood samples.

Results

Our data revealed that premorbid TS promoted significantly increased inflammation and loss of BBB integrity in TBI when compared to TS-Free test mice. Additionally, mice chronically exposed to TS before TBI experienced a more significant weight loss, behavioral and motor activity deficiency, and slower post-TBI recovery when compared to TS-free TBI mice.

Conclusion

The effects of premorbid TS appear consequential to the abrogation of physiological antioxidative and anti-inflammatory response to TBI leading to worsening impairments of the BBB, OS damage, and inflammation. These factors are also likely responsible for the retardation of post-traumatic recovery observed in these animals.
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Metadata
Title
The cerebrovascular and neurological impact of chronic smoking on post-traumatic brain injury outcome and recovery: an in vivo study
Authors
Farzane Sivandzade
Faleh Alqahtani
Ali Sifat
Luca Cucullo
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2020
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-020-01818-0

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