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

Raymond Shim, Jenny L. Wilson, Sarah E. Phillips, Gavin W. Lambert, Shu Wen Wen, Connie H.Y. Wong

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3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number100393
Number of pages10
JournalBrain, Behavior, & Immunity - Health
Volume18
DOIs
Publication statusPublished - Dec 2021

Keywords

  • Adrenergic
  • Infection
  • Stroke

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