Short-term Exposure to JUUL Electronic Cigarettes Can Worsen Ischemic Stroke Outcome by Disrupting the Blood-Brain Barrier

Background: The short and long-term health effects of JUUL electronic cigarette (e-Cig) are largely unknown and warrant extensive research. We hypothesized that chronic exposure to JUUL vapor could promote cerebrovascular toxicities impacting the progression and outcome of ischemic stroke to an extent comparable to that resulting from 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 that of 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. Similar to TS, exposure to JUUL downregulated the expression of the antioxidant Nrf2. The inflammatory marker ICAM-1 was also significantly upregulated by TS pre-exposure following tMCAO and by JUUL but to a lesser extent. Conclusions Our results suggest that JUUL exposure could negatively impact the cerebrovascular system as much as TS exposure.