Abstract
Byline: Hari Pradhyumnan, Neurology, Univ of Miami, Miami, FL; Shahil H Patel, Neurology, Univ of Miami, Miami, FL; Ofelia Furones-Alonso, Neurological Surgery, Univ of Miami, Miami, FL; Helen Bramlett, Neurological Surgery, Univ of Miami, Miami, FL; Ami P Raval, Neurology, Univ of Miami, Miami, FL Introduction: Smoking is a preventable risk factor for stroke and battery-operated nicotine delivery systems known as electronic cigarettes (EC) are popular. EC vapes aerosolize a mix of nicotine and chemicals forming harmful toxicants such as formaldehyde hemiacetal. Our understanding about effects of EC vaping on stroke outcome is limited. This study investigated effects of EC on global metabolic signature and stroke outcome in animals of both sexes. Methods: Sprague-Dawley rats (2-3 months old; n=8) of both sexes were randomly assigned either to air or EC vapor (5% nicotine Juul pods) exposure using the EcigAero-TM Aerosol Exposure Apparatus. Rats were exposed to air/EC for 16 nights. Per night, rats were exposed to 16 episodes of EC vapor. Each episode consisted of 2 seconds of Juul puffs followed by 8 seconds of air over the period of 8 minutes. After 16 days, the rats were divided into two cohorts. The first cohort of rats exposed to EC/Air was tested for cognitive capacities using the Morris water maze (WM) followed by brain collection for unbiased metabolomic (Metabolon Inc.) or Western blot analysis. The second cohort of rats exposed to EC/Air was subjected to transient middle cerebral artery occlusion (tMCAO; 90 min) or sham surgery and survived for 15-21 days. During the post-tMCAO survival, rats were tested for cognition using WM followed by brain collection for histopathological analysis. Results: Metabolomic analysis indicated that EC exposure resulted in significant increases (pëñ0.05) in phenylalanine and tryptophan metabolites, and both increases (pëñ0.05) and decreases (pëñ0.05) in histamine and tyrosine metabolites in the brains of female and male rats. Western blotting of rate-limiting enzymes in respective NT pathways corroborated the metabolomic data. Behavioral testing indicated worsened cognitive outcome in EC groups compared to air groups in rats of both sexes. Conclusion: EC vape exposure, even for as short as 2 weeks, impacts the metabolism of NT, induces cognitive deficits and worsens stroke outcomes in young male and female rats. Future studies investigating the impact of EC withdrawal on NT metabolism are needed to understand how long the deleterious effects of EC vaping persist in the brain.
