Short-term exposure to JUUL electronic cigarettes can worsen ischemic stroke outcome
Ali Ehsan Sifat, Sabrina Rahman Archie, Saeideh Nozohouri, Heidi Villalba, Yong Zhang, Sejal Sharma, Yashwardhan Ghanwatkar, Bhuvaneshwar Vaidya, D. Duncan Mara, Luca Cucullo, Thomas J. Abbruscato
Abstract
BACKGROUND: The short and long-term health effects of JUUL electronic cigarette (e-Cig) are largely unknown and warrant extensive research. We hypothesized that JUUL exposure could cause cerebrovascular toxicities impacting the progression and outcome of ischemic stroke comparable to tobacco smoke (TS) exposure. METHODS: We exposed male C57 mice to TS/JUUL vapor for 14 days. LCMS/MS was used to measure brain and plasma nicotine and cotinine level. Transient middle cerebral artery occlusion (tMCAO) followed by reperfusion was used to mimic ischemic stroke. Plasma levels of IL-6 and thrombomodulin were assessed by enzyme-linked immunosorbent assay. At the same time, western blotting was used to study blood-brain barrier (BBB) tight junction (TJ) proteins expression and key inflammatory and oxidative stress markers. RESULTS: tMCAO upregulated IL-6 and decreased plasma thrombomodulin levels. Post-ischemic brain injury following tMCAO was significantly worsened by JUUL/TS pre-exposure. TJ proteins expression was also downregulated by JUUL/TS pre-exposure after tMCAO. Like TS, exposure to JUUL downregulated the expression of the antioxidant Nrf2. ICAM-1 was upregulated in mice subjected to tMCAO following pre-exposure to TS or JUUL, with a greater effect of TS than JUUL. CONCLUSIONS: These results suggest that JUUL exposure could negatively impact the cerebrovascular system, although to a lesser extent than TS exposure.