Abstract
The global rise in nicotine-containing electronic cigarette (EC) use highlights the need to understand their impact on stroke outcomes. This study examined how EC exposure affects post-ischemic inflammation in adult Sprague-Dawley rats. Both sexes were exposed to air or EC vapor (5% nicotine Juul pods) for 16 nights, followed by transient middle cerebral artery occlusion (tMCAO; 90 min) or sham surgery. Animals were divided into two cohorts. In Cohort 1, RNA sequencing of ipsilateral cortex at 16 days post-tMCAO revealed 443 upregulated and 453 downregulated genes in males, and 537 upregulated and 578 downregulated genes in females (p<0.05). Differentially expressed genes in males were linked to membrane transport, signaling, and immune responses. In females, genes were enriched in pathways related to synaptic structure, cognition, proliferation, and genomic maintenance. In Cohort 2, microglial activation was analyzed 21 days post-tMCAO using Iba-1 immunostaining and Sholl analysis. EC-exposed females exhibited more de-ramified microglia, larger soma size, shorter branch length, and reduced morphological complexity compared to air-exposed controls. Current findings suggest that EC exposure exacerbates post-stroke neuroinflammation and transcriptomic dysregulation, particularly in females. Future studies should investigate whether withdrawal from EC reduces ischemic stroke severity and define the timeframe required for potential recovery.