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Tobacco smoke: a critical etiological factor for vascular impairment at the blood-brain barrier.

ABSTRACT: Active and passive tobacco smoke are associated with the dysfunction of endothelial physiology and vascular impairment. Studies correlating the effects of smoking and the brain microvasculature at the blood-brain barrier (BBB) level have been largely limited to few selective compounds that are present in the tobacco smoke (TS) yet the pathophysiology of smoking has not been unveiled. For this purpose, we characterized the physiological response of isolated human brain microvascular endothelial cells (HBMEC) and monocytes to the exposure of whole soluble TS extract. With the use of a well established humanized flow-based in vitro blood-brain barrier model (DIV-BBB) we have also investigated the BBB physiological response to TS under both normal and impaired hemodynamic conditions simulating ischemia. Our results showed that TS selectively decreased endothelial viability only at very high concentrations while not significantly affecting that of astrocytes and monocytes. At lower concentrations, despite the absence of cytotoxicity, TS induced a strong vascular pro-inflammatory response. This included the upregulation of endothelial pro-inflammatory genes, a significant increase of the levels of pro-inflammatory cytokines, activated matrix metalloproteinase, and the differentiation of monocytes into macrophages. When flow-cessation/reperfusion was paired with TS exposure, the inflammatory response and the loss of BBB viability were significantly increased in comparison to sham-smoke condition. In conclusion, TS is a strong vascular inflammatory primer that can facilitate the loss of BBB function and viability in pathological settings involving a local transient loss of cerebral blood flow such as during ischemic insults.

SUBMITTER: Hossain M

PROVIDER: S-EPMC2831230 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Tobacco smoke: a critical etiological factor for vascular impairment at the blood-brain barrier.

Hossain M M Sathe T T Fazio V V Mazzone P P Weksler Babette B Janigro D D Rapp E E Cucullo L L

Brain research 20090617

Active and passive tobacco smoke are associated with the dysfunction of endothelial physiology and vascular impairment. Studies correlating the effects of smoking and the brain microvasculature at the blood-brain barrier (BBB) level have been largely limited to few selective compounds that are present in the tobacco smoke (TS) yet the pathophysiology of smoking has not been unveiled. For this purpose, we characterized the physiological response of isolated human brain microvascular endothelial c ...[more]

PMID: 19539613

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Project description:Disruption of the blood-brain barrier has been proposed to be important in vascular cognitive impairment. Increased cerebrospinal fluid albumin and contrast-enhanced MRI provide supporting evidence, but quantification of the blood-brain barrier permeability in patients with vascular cognitive impairment is lacking. Therefore, we acquired dynamic contrast-enhanced MRI to quantify blood-brain barrier permeability in vascular cognitive impairment. Method- We studied 60 patients with suspected vascular cognitive impairment. They had neurological and neuropsychological testing, permeability measurements with dynamic contrast-enhanced MRI, and lumbar puncture to measure albumin index. Patients were separated clinically into subcortical ischemic vascular disease (SIVD), multiple and lacunar infarcts, and leukoaraiosis. Twenty volunteers were controls for the dynamic contrast-enhanced MRI studies, and control cerebrospinal fluid was obtained from 20 individuals undergoing spinal anesthesia for nonneurological problems.Thirty-six patients were classified as SIVD, 8 as multiple and lacunar infarcts, and 9 as leukoaraiosis. The albumin index was significantly increased in the SIVD group compared with 20 control subjects. Permeabilities for the patients with vascular cognitive impairment measured by dynamic contrast-enhanced MRI were significantly increased over control subjects (P<0.05). Patient age did not correlate with either the blood-brain barrier permeability or albumin index. Highest albumin index values were seen in the SIVD group (P<0.05) and were significantly increased over multiple and lacunar infarcts. K(i) values were elevated over control subjects in SIVD but were similar to multiple and lacunar infarcts.There was abnormal permeability in white matter in patients with SIVD as shown by dynamic contrast-enhanced MRI and albumin index. Future studies will be needed to determine the relationship of blood-brain barrier damage and development of white matter hyperintensities.

Dataset Information

Tobacco smoke: a critical etiological factor for vascular impairment at the blood-brain barrier.

Publications

Tobacco smoke: a critical etiological factor for vascular impairment at the blood-brain barrier.

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