Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world. It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD. The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected. The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors. In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity. In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke. We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress.

. (2016) Protective actions of des-acylated ghrelin on brain injury and blood-brain barrier disruption after stroke in mice. Clinical Science, 130(17), pp. 1545-1558. (doi:10.1042 This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/135040/ AbstractThe major ghrelin forms, acylated ghrelin and des-acylated ghrelin, are novel gastrointestinal hormones. Moreover, emerging evidence indicates that these peptides may have other functions including neuro-and vaso-protection. Here, we investigated whether post-stroke treatment with acylated ghrelin or des-acylated ghrelin could improve functional and histological endpoints of stroke outcome in mice after transient middle cerebral artery occlusion. We found that des-acylated ghrelin (1 mg/kg) improved neurological and functional performance, reduced infarct and swelling, and decreased apoptosis. In addition, it reduced BBB disruption in vivo and attenuated the hyper-permeability of mouse cerebral microvascular endothelial cells after oxygen glucose deprivation and reoxygenation (OGD + RO). By contrast, acylated ghrelin (1 mg/kg or 5 mg/kg) had no significant effect on these endpoints of stroke outcome. Next we found that des-acylated ghrelin's vasoprotective actions were associated with increased expression of tight junction proteins (occludin and claudin-5), and decreased cell death. Moreover, it attenuated superoxide production, Nox activity, and expression of 3-nitrotyrosine. Collectively, these results demonstrate that poststroke treatment with des-acylated ghrelin, but not acylated ghrelin, protects against ischemia/reperfusion-induced brain injury and swelling, and BBB disruption by reducing oxidative and/or nitrosative damage. Summary statementStroke is a leading cause of death, but treatments are limited. This experimental study reveals that the hormone ghrelin powerfully protects the brain and its blood vessels against injury after stroke, raising the possibility that it could be exploited therapeutically. Short titleDes-acylated ghrelin protects against stroke. KeywordsIschemia, reperfusion, ghrelin, neuroprotection, blood-brain barrier. Abbreviations listBlood-brain barrier (BBB); ghrelin O-acyltransferase (GOAT); growth hormone secretagogue receptor 1a (GHSR1a); oxygen glucose deprivation and reoxygenation (OGD + Clinical perspectives• Ischemic stroke is a leading cause of mortality and long-term disability, but treatment options are limited. The major ghrelin forms, acylated ghrelin and des-acylated ghrelin, are novel gastrointestinal hormones. Moreover, recent evidence indicates these peptides may have neuroprotective and vasoprotective actions, and thus may protective actions in ischemic stroke.• In this study we tested whether the peptides could mediate protection in a clinically relevant mouse model of ischemic stroke.• Our findings reveal protective actions of des-acylated ghrelin whe...

Stroke is a major cause of death worldwide and ischemic stroke is the most common subtype accounting for approximately 80% of all cases. Pulmonary complications occur in the first few days to weeks following ischemic stroke and are a major contributor to morbidity and mortality. Acute lung injury (ALI) occurs in up to 30% of patients with subarachnoid haemorrhage but the incidence of ALI after ischemic stroke is unclear. As ischemic stroke is the most common subtype of stroke, it is important to understand the development of ALI following the initial ischemic injury to the brain. Therefore, this study investigated whether focal ischemic stroke causes lung inflammation and ALI in mice. Ischemic stroke caused a significant increase in bronchoalveolar lavage fluid (BALF) macrophages and neutrophils and whole lung tissue proinflammatory IL-1β mRNA expression but this did not translate into histologically evident ALI. Thus, it appears that lung inflammation, but not ALI, occurs after experimental ischemic stroke in mice. This has significant implications for organ donors as the lungs from patient’s dying of ischemic stroke are not severely damaged and could thus be used for transplantation in people awaiting this life-saving therapy.

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.