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

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 OPEN ACCESS Int. J. Environ. Res. Public Health 2010, 7 4112TS 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".

Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress

“…[111][112][113] As shown in Figure 4, a acute or chronic TS exposure significantly elevates endothelial oxidative and nitrosative stress responses resulting in a progressive loss of BBB integrity. 21 For example, using static or flow-based in vitro BBB models, we previously demonstrated a marked increase in intracellular ROS/RNS and secretory profile of various pro-inflammatory markers accompanied by alterations in BBB TJ protein expression and re-distribution following TS exposure. 43,114 In addition, DNA microarray-based global transcriptome profiling indicated a rapid and transient up-regulation of Nrf2 and its downstream anti-oxidant molecular networks in response to prolonged TS exposure in brain microvascular endothelial cultures.…”

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“…8 There is a growing body of evidence that oxidants such as reactive oxygen species are involved in the development of cerebrovascular degenerative diseases, hypertension, increased oxidative stress, impaired nitric oxide bioavailability and endothelial dysfunction. 9,10 Production of reactive oxygen species in quantities that overwhelm the endogenous antioxidant defense system is referred to as oxidative stress and involves the oxidation of molecules in ways that impair cellular function. 11 Numerous epidemiological studies have shown that cigarette smoking causes oxidative stress, impaired antioxidant blood levels, increased risk of cancer, cardiovascular diseases, diabetes, pulmonary hypertension, stroke and premature deaths.…”

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“…Nitric oxide is a critical factor that besides affecting the vascular tone also modulates platelet aggregation and leukocyte adhesion to the endothelium. At the BBB, NO plays an inhibitory role in the dynamic regulation of BBB function 132,133 and is involved in a variety of physiologic and pathological processes as part of the inflammation process itself 134 . Cigarette smoke can also modulate the level of NO by decreasing the activity of eNOS and promoting that of its inducible form (iNOS) 135 .…”