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Open Access Highly Accessed Research article

In Vitro Assessment of Tobacco Smoke Toxicity at the BBB: Do Antioxidant Supplements Have a Protective Role?

Mohammed Hossain12, Peter Mazzone3, William Tierney4 and Luca Cucullo5*

Author Affiliations

1 Cerebrovascular Research Department of Pulmonary Medicine, Cleveland Clinic, Cleveland, OH 44195 USA

2 Department of Cell Biology Department of Pulmonary Medicine, Cleveland Clinic, Cleveland, OH 44195 USA

3 Department of Pulmonary Medicine, Cleveland Clinic, Cleveland, OH 44195 USA

4 Case Western Reserve University, Cleveland, OH 44106 USA

5 Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX 79106 USA

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BMC Neuroscience 2011, 12:92  doi:10.1186/1471-2202-12-92

Published: 24 September 2011



Tobacco smoke (TS) contains highly reactive oxygen species (such as hydrogen peroxide, peroxynitrite, etc), which cause oxidative damage in vascular tissue and may exacerbate inflammatory events leading to the blood-brain barrier damage (BBBD) which accompanies the development of a variety of neurological disorders. Smokers often have elevated leukocyte counts (primarily neutrophils and monocytes), and significant decreases in plasma alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) levels due to increased anti-oxidative mobilization in response to oxidative stress evoked by TS. For this purpose, using static culture systems and a well-established dynamic in vitro BBB model (DIV-BBB) we tested the hypothesis that antioxidant vitamin supplementation (E and/or C) can protect the BBB during exposure to whole soluble TS.


TS exacerbates inflammatory events and leads to endothelial overexpression of vascular adhesion molecules (VCAM-1, P-selectin and E-selectin), release of pro-inflammatory cytokines (TNF-α and IL-6) and nitric oxide (NO), release and activation of matrix metalloproteinases (MMP-2 and MMP-9), monocytic maturation into macrophages, and adhesion to the vascular endothelium. Furthermore, TS altered the normal glucose metabolic behaviour of in vitro BBB capillaries and caused a period of transient anaerobic respiration to meet the cellular bioenergetic demand. Pre-treatment with antioxidant vitamins (C and/or E) effectively reduced the pro-inflammatory activity associated with TS, protecting the viability and functions of the BBB.


Our results have shown that loss of endothelial viability as well as BBB function and integrity caused by TS exposure can be prevented or at least reduced by normal physiologic concentrations of antioxidant vitamins in vitro.