# Testing Tobacco Smoke and e-Cigarette Toxicity at the Blood-Brain Barrier

> **NIH NIH R01** · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · 2020 · $113,362

## Abstract

Abstract: 
In the past decade a number of alternative vaping products have hit the market, rapidly gaining consumers among adults
and, especially, adolescents. Electronic nicotine delivery systems or e-cigarettes (e-Cigs) have become the sought-after
product due to the belief that they are much safer than traditional cigarettes. Moreover, tobacco smoking (TS) is
associated with vascular endothelial dysfunction in a causative and dose dependent manner primarily related to the TS
content of reactive oxygen species (ROS), nicotine, and oxidative stress (OS) -driven inflammation. Current scientific
opinion considers OS-mediated pathways to play a major role in the pathogenesis of these disorders, especially stroke.
Preclinical studies (and preliminary data presented herein) have shown that nicotine (the principal e-liquid's ingredient)
can cause OS, exacerbation of cerebral ischemia and secondary brain injury. Likewise, chronic e-Cig vaping could be
prodromal to cerebrovascular impairment and promote cerebrovascular conditions that favor the onset of stroke and post-
ischemic brain injury, suggested by our initial findings. The health impact of e-Cig vaping is currently unknown and the
limited research and dearth of regulatory guidelines for the content of the vaping solution for e-Cigs (various harmful
compounds including aldehydes, nitrosamines etc. have been detected in the e-Cig vapors) has become a critical public
and regulatory concern we also want to address with this research. Further, we and others have found that TS promotes
glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other
pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation,
inflammation, and blood-brain barrier (BBB) impairment. Recent in vitro findings and preliminary data from our group,
supports an additive release pattern of angiogenic, oxidative and inflammatory factors by BBB endothelial cells in
response to hyperglycemia (HG) and/or stroke conditions with comcomitant exposure to cigarette smoke extracts (CSE),
thus suggesting the involvement of common pathogenic modulators of BBB impairment. To this end, metformin (MF; a
widely prescribed, firstline anti-diabetic drug) before and after stroke injury has been shown to reduces stress and inhibits
inflammatory responses 88. Recent preliminary data revealed that MF activates counteractive mechanisms which
drastically reduce TS toxicity at the level of the BBB. These beneficial effects have been shown to be mediated by MF
activation of nuclear factor erythroid 2-related factor (Nrf2) 51. Our hypothesis is that excessive OS caused by TS and e-
Cigs dysregulation of the cellular antioxidant response system is the linking underling mechanism prodromal to
cerebrovascular toxicity and highten risk and/or severity of stroke
In this respect we will: 1) Assess the potential cerebrovascular pathogenic impact of e-Ci...

## Key facts

- **NIH application ID:** 10132443
- **Project number:** 3R01DA029121-10S1
- **Recipient organization:** TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
- **Principal Investigator:** Thomas J Abbruscato
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $113,362
- **Award type:** 3
- **Project period:** 2011-03-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132443

## Citation

> US National Institutes of Health, RePORTER application 10132443, Testing Tobacco Smoke and e-Cigarette Toxicity at the Blood-Brain Barrier (3R01DA029121-10S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10132443. Licensed CC0.

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