Nicotine aggravates the brain postischemic inflammatory response.
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 ∼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-1β, TNF-α, 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.
Department of Pathology, University of Michigan, Medical School, Ann Arbor, 48109-0532, USA.
Shayna T
ST
Bradford
Svetlana M
SM
Stamatovic
Raj S
RS
Dondeti
Richard F
RF
Keep
Anuska V
AV
Andjelkovic
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000473:pathology; D020520:Brain Infarction / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D004660:Encephalitis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000009:adverse effects* / Q000097:blood; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D053583:Interleukin-1beta; D009538:Nicotine
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