Ma, Oliver B., Noack, Timothy C., Trollope, Alexandra F., and Moxon, Joseph V. (2026) A systematic review and meta-analysis assessing the influence of histone deacetylase 6 inhibition on brain infarction and neurological function following acute ischaemic stroke in rodent models. Journal of Cerebral Blood Flow & Metabolism. (In Press)

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Abstract

Histone deacetylase (HDAC) inhibition has been suggested to improve stroke outcomes, however, pan-HDAC inhibition can cause adverse effects. Individual studies report that specifically inhibiting HDAC6 may improve stroke outcomes. This article aimed to quantify the impact of pharmacologically inhibiting HDAC6 on cerebral infarction size and neurological function within in vivo stroke models. Seven studies fulfilled inclusion criteria. Meta-analysis demonstrated that animals receiving HDAC6 inhibitors developed significantly smaller cerebral infarctions than controls (standardised mean difference −1.25, 95% confidence intervals: −1.68, −0.81). This was upheld in sub-analyses comparing different species, and groups receiving HDAC6 inhibitors shortly after stroke, or after a 24 h delay. Modelling analyses demonstrated that animals receiving HDAC6 inhibitors during the hyperacute phase of stroke had significantly better functional outcomes, whereas sub-acute HDAC6 inhibition impaired recovery. Despite a small evidence base, findings suggest that HDAC6 inhibition within 24 h of stroke onset may improve outcomes. Current understanding is limited by male bias in existing studies and a lack of assessment in models incorporating stroke comorbidities or risk factors. Studies employing randomised controlled trial principles, and detailed assessment of the molecular and physiological mechanisms underpinning reported cytoprotection are warranted to assess clinical potential pharmacological HDAC6 inhibition to improve stroke management.

Item ID:	90308
Item Type:	Article (Research - C1)
ISSN:	1559-7016
Copyright Information:	CC BY.
Date Deposited:	19 Jan 2026 23:10
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320101 Cardiology (incl. cardiovascular diseases) @ 100%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200102 Efficacy of medications @ 100%
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