Abstract
Cigarette smoking is a risk factor for stroke and is linked to stroke severity. Previous studies have shown that cigarette smoke extract (CSE) triggers endothelial dysfunction in vitro by initiating oxidative stress and/or an inflammatory response. In addition, cerebral endothelial dysfunction (particularly at the level of the blood-brain barrier [BBB]) contributes to stroke pathogenesis. Therefore, we hypothesized that cigarette smoking may influence stroke, at least in part, by exacerbating ischaemia-induced BBB disruption. To test this, we examined the effect of CSE on the permeability of cerebral endothelial cells exposed to oxygen glucose deprivation and reoxygenation (OGD + RO). We found that the loss of BBB integrity following ischaemic/reperfusion-like conditions was significantly worsened by CSE. Despite this being associated with increased mRNA expression of Nox catalytic subunits, reactive oxygen species (ROS) levels were however markedly lower. Furthermore, this occurred in association with elevated expression of antioxidant enzymes (SOD1, SOD2, and Gpx-1), suggesting an antioxidant defence response. Lastly, we found that CSE significantly upregulated mRNA expression of cytokines (IL-6 and TGF-β). Collectively, these results show that acute exposure to CSE worsens BBB disruption caused by OGD + RO, however, this is not linked to elevated ROS levels but may involve inflammatory mechanisms.
Highlights
Cigarette smoking is a risk factor for stroke and is linked to stroke severity
The aim of this study was to examine whether cigarette smoke extract (CSE) worsens blood-brain barrier (BBB) disruption using a well-established in vitro BBB stroke model, and to determine whether this is associated with elevated reactive oxygen species (ROS) production and/or inflammation
20% or 40% CSE resulted in a loss of their typical spindle-shape appearance as well as visible cell retraction (Fig. 2A). 5, 10, or 20% CSE had no significant effect on the viability of either normoxic or Oxygen glucose deprivation (OGD) + RO bEnd.[3] cells relative to vehicle-treated cells (Fig. 2B,C, P > 0.05, n = 6–8), whereas 40% CSE decreased cell viability by ~50% (Fig. 2B,C, P < 0.05)
Summary
Cigarette smoking is a risk factor for stroke and is linked to stroke severity. Previous studies have shown that cigarette smoke extract (CSE) triggers endothelial dysfunction in vitro by initiating oxidative stress and/or an inflammatory response. We found that the loss of BBB integrity following ischaemic/reperfusion-like conditions was significantly worsened by CSE Despite this being associated with increased mRNA expression of Nox catalytic subunits, reactive oxygen species (ROS) levels were markedly lower. We found that CSE significantly upregulated mRNA expression of cytokines (IL-6 and TGF-β) These results show that acute exposure to CSE worsens BBB disruption caused by OGD + RO, this is not linked to elevated ROS levels but may involve inflammatory mechanisms. Cigarette smoke contains over 4,000 chemicals including nicotine and reactive oxygen species (ROS, e.g. superoxide, hydrogen peroxide)[11] These oxidants give rise to secondary ROS by inflammatory cells within the lung as part of an inflammatory-immune response towards a pathogen or irritant[6]. The aim of this study was to examine whether CSE worsens BBB disruption using a well-established in vitro BBB stroke model, and to determine whether this is associated with elevated ROS production and/or inflammation
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