Pathophysiological Impact of Cigarette Smoke Exposure on the Cerebrovascular System with a Focus on the Blood-brain Barrier: Expanding the Awareness of Smoking Toxicity in an Underappreciated Area

Damir Janigro,Mohammed Hossain,William Tierney,Luca Cucullo,Vikram Puvenna,Peter Mazzone

doi:10.3390/ijerph7124111

Abstract

Recent evidence has indicated that active and passive cigarette smoking are associated, in a dose-dependent manner, with dysfunction of normal endothelial physiology. Tobacco smoke (TS) may predispose individuals to atherogenic and thrombotic problems, significantly increasing the risk for ischemic manifestations such as acute coronary syndrome and stroke. Despite the strong evidence for an association between smoking and vascular impairment, the impact of TS exposure on the blood-brain barrier (BBB) has only been marginally addressed. This is a major problem given that the BBB is crucial in the maintenance of brain homeostasis. Recent data have also shown that chronic smokers have a higher incidence of small vessel ischemic disease (SVID), a pathological condition characterized by leaky brain microvessels and loss of BBB integrity. In the brain TS increases the risk of silent cerebral infarction (SCI) and stroke owing to the pro-coagulant and atherogenic effects of smoking. In this article we provide a detailed review and analysis of current knowledge of the pathophysiology of tobacco smoke toxicity at the cerebrovascular levels. We also discuss the potential toxicity of recently marketed “potential-reduced exposure products”.

Highlights

IntroductionA great deal is known about the pathophysiologic and clinical effects of tobacco smoke exposure
A great deal is known about the pathophysiologic and clinical effects of tobacco smoke exposure.Tobacco smoke exposure is responsible for a large portion of the preventable deaths worldwide.Knowledge of its impact on vascular health, related to cardiac disease, is well established.Less well described are the mechanisms of tobacco smoke induced vascular damage in the cerebrovascular system, as they apply to the blood brain barrier.2
Despite the crucial importance of the blood-brain barrier (BBB) and the strong scientific and clinical evidence for an association between Tobacco smoke (TS) exposure and vascular impairment, the effects of smoking on the BBB have been only marginally addressed and studies have been limited to a handful of substances among the multitudes found in cigarette smoke

Summary

Introduction

A great deal is known about the pathophysiologic and clinical effects of tobacco smoke exposure. Tobacco smoke exposure is responsible for a large portion of the preventable deaths worldwide. Knowledge of its impact on vascular health, related to cardiac disease, is well established. Less well described are the mechanisms of tobacco smoke induced vascular damage in the cerebrovascular system, as they apply to the blood brain barrier

Tobacco Smoke Induces Oxidative Injury to the Cerebrovascular System

Tobacco Smoke Induces Inflammatory and Thrombotic Injury

Pathophysiology of BBB Endothelial Cells

Vascular and Inflammatory Effects of Tobacco Smoke on the BBB

Consequences of TS Induced Damage

New Tobacco Products

Findings

Conclusions