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Implications of MMP-12 in the pathophysiology of ischaemic stroke
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Implications of MMP-12 in the pathophysiology of ischaemic stroke
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Journal Article
Implications of MMP-12 in the pathophysiology of ischaemic stroke
2024
Overview
This article focuses on the emerging role of matrix metalloproteinase-12 (MMP-12) in ischaemic stroke (IS). MMP-12 expression in the brain increases dramatically in animal models of IS, and its suppression reduces brain damage and promotes neurological, sensorimotor and cognitive functional outcomes. Thus, MMP-12 could represent a potential target for the management of IS. This article provides an overview of MMP-12 upregulation in the brain following IS, its deleterious role in the post-stroke pathogenesis (blood-brain barrier disruption, inflammation, apoptosis and demyelination), possible molecular interactions and mechanistic insights, its involvement in post-ischaemic functional deficits and recovery as well as the limitations, perspectives, challenges and future directions for further research. Prior to testing any MMP-12-targeted therapy in patients with acute IS, additional research is needed to establish the effectiveness of MMP-12 suppression against IS in older animals and in animals with comorbidities. This article also examines the clinical implications of suppressing MMP-12 alone or in combination with MMP-9 for extending the currently limited tissue plasminogen activator therapy time window. Targeting of MMP-12 is expected to have a profound influence on the therapeutic management of IS in the future.
Publisher
BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
Subject
/ brain
/ Humans
/ Hypoxia
/ Ischemia
/ Ischemic Stroke - drug therapy
/ Ischemic Stroke - enzymology
/ Ischemic Stroke - metabolism
/ Ischemic Stroke - physiopathology
/ Matrix Metalloproteinase 12 - metabolism
/ Matrix Metalloproteinase Inhibitors - pharmacology
/ Matrix Metalloproteinase Inhibitors - therapeutic use
/ Proteins
/ Review
/ Stroke
