The role of β2 adrenergic receptor on infection development after ischaemic stroke

Mechanisms underlying post-stroke immune impairments and subsequent development of fatal lung infection have been suggested to involve multiple pathways, including hyperactivation of the sympathetic nervous system (SNS), which results in the excessive release of catecholamines and activation of β-ad...

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Autores principales:	Raymond Shim, Jenny L. Wilson, Sarah E. Phillips, Gavin W. Lambert, Shu Wen Wen, Connie H.Y. Wong
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Stroke Infection Adrenergic Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/81df3de78dd146d69b514e10bf419e72
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spelling	oai:doaj.org-article:81df3de78dd146d69b514e10bf419e722021-11-28T04:38:42ZThe role of β2 adrenergic receptor on infection development after ischaemic stroke2666-354610.1016/j.bbih.2021.100393https://doaj.org/article/81df3de78dd146d69b514e10bf419e722021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666354621001964https://doaj.org/toc/2666-3546Mechanisms underlying post-stroke immune impairments and subsequent development of fatal lung infection have been suggested to involve multiple pathways, including hyperactivation of the sympathetic nervous system (SNS), which results in the excessive release of catecholamines and activation of β-adrenergic receptors (βARs). Indeed, previous reports from experimental studies demonstrated that post-stroke infection can be inhibited with treatment of β-blockers. However, the effectiveness of β-blockers in reducing post-stroke infection has yielded mixed results in retrospective clinical trials and its use remain controversial. In this study, we performed mid-cerebral artery occlusion in mice either genetically deficient in β2-adrenergic receptor (β2AR) or treated with non-selective and selective βAR antagonists to explore the contributions of the SNS in the development of post-stroke lung infection. Stroke induced a systemic activation of the SNS as indicated by elevated levels of plasma catecholamines and UCP-1 activity. However, β2AR deficient mice showed similar degrees of post-stroke immune impairment and infection rate compared to wildtype counterparts, potentially due to compensatory mechanisms common in transgenic animals. To overcome this, we treated post-stroke wildtype mice with pharmacological inhibitors of the βARs, including the non-selective antagonist propranolol (PPL) and selective β2AR antagonist ICI-118551. Both pharmacological strategies to block the action of SNS signalling were unable to reduce infection in mice that underwent ischaemic stroke. Overall, our data suggests that other mechanisms independent or in combination with β2AR activation contribute to the development of post-stroke infection.Raymond ShimJenny L. WilsonSarah E. PhillipsGavin W. LambertShu Wen WenConnie H.Y. WongElsevierarticleStrokeInfectionAdrenergicNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENBrain, Behavior, & Immunity - Health, Vol 18, Iss , Pp 100393- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Stroke Infection Adrenergic Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Stroke Infection Adrenergic Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Raymond Shim Jenny L. Wilson Sarah E. Phillips Gavin W. Lambert Shu Wen Wen Connie H.Y. Wong The role of β2 adrenergic receptor on infection development after ischaemic stroke
description	Mechanisms underlying post-stroke immune impairments and subsequent development of fatal lung infection have been suggested to involve multiple pathways, including hyperactivation of the sympathetic nervous system (SNS), which results in the excessive release of catecholamines and activation of β-adrenergic receptors (βARs). Indeed, previous reports from experimental studies demonstrated that post-stroke infection can be inhibited with treatment of β-blockers. However, the effectiveness of β-blockers in reducing post-stroke infection has yielded mixed results in retrospective clinical trials and its use remain controversial. In this study, we performed mid-cerebral artery occlusion in mice either genetically deficient in β2-adrenergic receptor (β2AR) or treated with non-selective and selective βAR antagonists to explore the contributions of the SNS in the development of post-stroke lung infection. Stroke induced a systemic activation of the SNS as indicated by elevated levels of plasma catecholamines and UCP-1 activity. However, β2AR deficient mice showed similar degrees of post-stroke immune impairment and infection rate compared to wildtype counterparts, potentially due to compensatory mechanisms common in transgenic animals. To overcome this, we treated post-stroke wildtype mice with pharmacological inhibitors of the βARs, including the non-selective antagonist propranolol (PPL) and selective β2AR antagonist ICI-118551. Both pharmacological strategies to block the action of SNS signalling were unable to reduce infection in mice that underwent ischaemic stroke. Overall, our data suggests that other mechanisms independent or in combination with β2AR activation contribute to the development of post-stroke infection.
format	article
author	Raymond Shim Jenny L. Wilson Sarah E. Phillips Gavin W. Lambert Shu Wen Wen Connie H.Y. Wong
author_facet	Raymond Shim Jenny L. Wilson Sarah E. Phillips Gavin W. Lambert Shu Wen Wen Connie H.Y. Wong
author_sort	Raymond Shim
title	The role of β2 adrenergic receptor on infection development after ischaemic stroke
title_short	The role of β2 adrenergic receptor on infection development after ischaemic stroke
title_full	The role of β2 adrenergic receptor on infection development after ischaemic stroke
title_fullStr	The role of β2 adrenergic receptor on infection development after ischaemic stroke
title_full_unstemmed	The role of β2 adrenergic receptor on infection development after ischaemic stroke
title_sort	role of β2 adrenergic receptor on infection development after ischaemic stroke
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/81df3de78dd146d69b514e10bf419e72
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The role of β2 adrenergic receptor on infection development after ischaemic stroke

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