Prior cigarette smoke exposure does not affect acute post-stroke outcomes in mice

Abstract

Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death globally and is characterized by airflow limitation that is progressive and not fully reversible. Cigarette smoking is the major cause of COPD. Fifty percent of deaths in the COPD population are due to a cardiovascular event and it is now recognised that COPD is a risk factor for stroke. Whether COPD increases stroke severity has not been explored. The aim of this study was to investigate whether functional and histological endpoints of stroke outcomes in mice after transient middle cerebral artery occlusion (tMCAo) were more severe in mice exposed to cigarette smoke (CS). 7-week-old male C57BL/6 mice were exposed to room air or CS generated from 9 cigarettes/day, 5 days/week for 2, 8 and 12 weeks. Following air or CS exposure, mice underwent tMCAO surgery with an ischaemic period of 30–40 min or sham surgery. Mice were euthanised 24 h following the induction of ischaemia and bronchoalveolar lavage fluid (BALF), lungs and brains collected. Mice exposed to CS for 2 weeks and subjected to a stroke had similar BALF macrophages to air-exposed and stroke mice. However, CS plus stroke mice had significantly more BALF total cells, neutrophils and lymphocytes than air plus stroke mice. Mice exposed to CS for 8 and 12 weeks had significantly greater BALF total cells, macrophages, neutrophils and lymphocytes than air-exposed mice, but stroke did not affect CS-induced BALF cellularity. Prior CS exposure did not worsen stroke-induced neurological deficit scores, reduced foregrip strength, infarct and oedema volumes. Collectively, we found that although CS exposure caused significant BALF inflammation, it did not worsen acute post-stroke outcomes in mice. This data suggests that while patients with COPD are at increased risk of stroke, it may not translate to COPD patients having more severe stroke outcomes.

Losartan does not inhibit cigarette smoke-induced lung inflammation in mice

“…Consistent with our previous studies 33,34 , we found in this study that mice exposed to CS had a significant increase in total inflammatory cells in the BALF, which was largely attributed to increased macrophages and neutrophils. Human studies have also shown that COPD patients have increased macrophages in BALF, sputum, airways and lung parenchyma compared to healthy individuals 2 .…”

Exposure to Cigarette Smoke Augments Post-ischemic Brain Injury and Inflammation via Mobilization of Neutrophils and Monocytes

“…It's notable that the influences of cigarette smoke on stroke severity may be affected by the length of exposure duration and exposure dose. A recent study reported that cigarette smoke exposure at a dose of nine cigarettes per day had no significant impact on brain infarction or neurological deficits in mice subjected to 30–40 min MCAO (32). The reasons that caused this discrepancy may be at least partially caused by the different exposure protocol of cigarette smoke and ischemia duration.…”