# Injury of blood brain and alveolar-endothelial barriers caused by alcohol and electronic cigarettes via purinergic receptor signaling

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2024 · $608,357

## Abstract

Polydrug abuse (especially alcohol use disorder, AUD, and smoking) are known individually to
compromise the lung alveolar-endothelial barrier (AEB) and the blood brain barrier (BBB). Very
limited knowledge exists regarding damage in lung and brain due to electronic cigarettes (e-Cig)
in combination with AUD. E-Cig have become popular, yet very limited data indicate that they
cause endothelial dysfunction and result in a pro-inflammatory phenotype in macrophages and
endothelium in lungs. While e-Cig are known to be addictive, their effects on the brain and
cognition are essentially unknown. Our data show that chronic e-Cig exposure in mice
enhanced permeability of the BBB and neuroinflammation, diminished expression of a key
glucose transporter and tight junction protein on brain endothelium, and impaired cognition.
Preliminary data indicate that the combination of alcohol/e-Cig exposure in vivo caused
enhanced AEB permeability and amplified neuroinflammation/BBB compromise. We found that
e-Cig and alcohol impair AEB and BBB via the same mechanism including mitochondrial
dysfunction, Ca2+ accumulation, and ATP extracellular release, potentially mediated by
purinergic receptor, P2X7, in cellular components of AEB/BBB. Using innovative in vitro 3D
systems of AEB and BBB and relevant animal models, we test the hypothesis that BBB and
AEB injury in e-Cig/alcohol exposure are mediated through the P2X7 receptor. In aim 1, we will
screen the magnitude of injury (mitochondrial dysfunction, Ca2+ increase and ATP release) by
various types of e-Cig in combination with alcohol on human brain and lung endothelial and lung
epithelial cells. Then, we will define mechanisms of demise using innovative 3D in vitro
constructs of lung and brain microvasculature, functional assays, assessment of mitochondrial
functions and expression of key molecules supporting BBB and AEB. We will investigate the
contribution of activation of the purinergic P2X7 receptor in e-Cig/alcohol induced BBB/AEB
dysfunction. The 2nd aim will study in vivo lung injury after chronic alcohol feeding and e-Cig
vaping evaluating AEB permeability, expression of barrier supporting molecules, inflammatory
responses (immunohistochemistry, protein/mRNA, bronchoalveolar lavage). P2X7 knockout
(KO) animals will allow dissection of the role of this receptor in pulmonary dysfunction. The 3rd
aim will decipher combined in vivo effects of BBB function, expression of barrier-mediating
molecules, and neuroinflammation. The same experiments performed in P2X7 KO mice will
determine the importance of this pathway in CNS injury. Markers of lung injury and BBB
damage will be measured in blood and correlated with signs of end-organ pathology.

## Key facts

- **NIH application ID:** 10892785
- **Project number:** 5R01AA030841-02
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Yuri Persidsky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $608,357
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892785

## Citation

> US National Institutes of Health, RePORTER application 10892785, Injury of blood brain and alveolar-endothelial barriers caused by alcohol and electronic cigarettes via purinergic receptor signaling (5R01AA030841-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10892785. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*