The Impact of Nicotine along with Oral Contraceptive Exposure on Brain Fatty Acid Metabolism in Female Rats.

Smoking-derived nicotine (N) and oral contraceptive (OC) synergistically exacerbate ischemic brain damage in females, and the underlying mechanisms remain elusive. In a previous study, we showed that N + OC exposure altered brain glucose metabolism in females. Since lipid metabolism complements glycolysis, the current study aims to examine the metabolic fingerprint of fatty acids in the brain of female rats exposed to N+/-OC. Adolescent and adult Sprague-Dawley female rats were randomly (n = 8 per group) exposed to either saline or N (4.5 mg/kg) +/-OC (combined OC or placebo delivered via oral gavage) for 16-21 days. Following exposure, brain tissue was harvested for unbiased metabolomic analysis (performed by Metabolon Inc., Morrisville, NC, USA) and the metabolomic profile changes were complemented with Western blot analysis of key enzymes in the lipid pathway. Metabolomic data showed significant accumulation of fatty acids and phosphatidylcholine (PC) metabolites in the brain. Adolescent, more so than adult females, exposed to N + OC showed significant increases in carnitine-conjugated fatty acid metabolites compared to saline control animals. These changes in fatty acyl carnitines were accompanied by an increase in a subset of free fatty acids, suggesting elevated fatty acid ß-oxidation in the mitochondria to meet energy demand. In support, ß-hydroxybutyrate was significantly lower in N + OC exposure groups in adolescent animals, implying a complete shunting of acetyl CoA for energy production via the TCA cycle. The reported changes in fatty acids and PC metabolism due to N + OC could inhibit post-translational palmitoylation of membrane proteins and synaptic vesicle formation, respectively, thus exacerbating ischemic brain damage in female rats.

Impact of Electronic Cigarette Vaping on Cerebral Ischemia: What We Know So Far.

Electronic cigarettes (ECs) are battery-powered nicotine delivery devices that have rapidly gained popularity and attention globally. ECs work by heating a liquid to produce an aerosol that usually contains nicotine, flavoring compounds, and other chemicals, which are inhaled during vaping. EC aerosols are depicted to contain a lower number and overall quantity of harmful toxicants than conventional cigarettes (CCs). However, emerging research indicates that EC aerosols contain harmful ingredients including ultrafine particles, volatile organic compounds, and heavy metals. One common ingredient found in both CCs and ECs is nicotine, which has been shown to be both highly addictive and toxic. Particularly relevant to our current review, there is an enormous amount of literature that shows that smoking-derived nicotine exacerbates ischemic brain damage. Therefore, the question arises: will EC use impact the outcome of stroke? ECs are highly popular and relatively new in the market; thus, our understanding about the long-term effects of EC use on brain are lacking. The current review strives to extrapolate the existing understanding of the nicotine-induced effects of conventional smoking on the brain to the possible effects that ECs may have on the brain, which may ultimately have a potential for adverse stroke risk or severity.