Nicotine aggravates the brain postischemic inflammatory response

Bradford ST, Stamatovic SM, Dondeti RS, Keep RF, Andjelkovic AV. Nicotine aggravates the brain postischemic inflammatory response. Am J Physiol Heart Circ Physiol 300: H1518-H1529, 2011. First published January 14, 2011; doi:10.1152/ajpheart.00928.2010.-A substantial body of evidence suggests that nicotine adversely affects cerebral blood flow and the blood-brain barrier and is a risk factor for stroke. The present study investigated the effect of nicotine on cerebrovascular endothelium under basal and ischemia/reperfusion injury under in vivo condition. Nicotine (2 mg/kg sc) was administered to mice over 14 days, which resulted in plasma nicotine levels of similar to 100 ng/ml, reflecting plasma concentrations in average to heavy smokers. An analysis of the phenotype of isolated brain microvessels after nicotine exposure indicated higher expression of inflammatory mediators, cytokines (IL-1 beta, TNF-alpha, and IL-18), chemokines (CCL2 and CX(3)CL1), and adhesion molecules (ICAM-1, VCAM-1, and P-selectins), and this was accompanied by enhanced leukocyte infiltration into brain during ischemia/reperfusion (P < 0.01). Nicotine had a profound effect on ischemia/reperfusion injury; i.e., increased brain infarct size (P < 0.01), worse neurological deficits, and a higher mortality rate. These experiments illuminate, for the first time, how nicotine regulates brain endothelial cell phenotype and postischemic inflammatory response at the brain-vascular interface.