A systematic review and in silico analysis of studies investigating the ischaemic penumbra proteome in animal models of experimental stroke

Moxon, Joseph V., Pretorius, Cornea, Trollope, Alexandra F., Mittal, Parul, Klingler-Hoffmann, Manuela, Hoffmann, Peter, and Golledge, Jonathan (2024) A systematic review and in silico analysis of studies investigating the ischaemic penumbra proteome in animal models of experimental stroke. Journal of Cerebral Blood Flow & Metabolism. (In Press)

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Abstract

Ischaemic stroke results in the formation of a cerebral infarction bordered by an ischaemic penumbra. Characterising the proteins within the ischaemic penumbra may identify neuro-protective targets and novel circulating markers to improve patient care. This review assessed data from studies using proteomic platforms to compare ischaemic penumbra tissues to controls following experimental stroke in animal models. Proteins reported to differ significantly between penumbra and control tissues were analysed in silico to identify protein-protein interactions and over-represented pathways. Sixteen studies using rat (n = 12), mouse (n = 2) or primate (n = 2) models were included. Heterogeneity in the design of the studies and definition of the penumbra were observed. Analyses showed high abundance of p53 in the penumbra within 24 hours of permanent ischaemic stroke and was implicated in driving apoptosis, cell cycle progression, and ATM- MAPK- and p53- signalling. Between 1 and 7 days after stroke there were changes in the abundance of proteins involved in the complement and coagulation pathways. Favourable recovery 1 month after stroke was associated with an increase in the abundance of proteins involved in wound healing. Poor recovery was associated with increases in prostaglandin signalling. Findings suggest that p53 may be a target for novel therapeutics for ischaemic stroke.

Item ID: 82633
Item Type: Article (Research - C1)
ISSN: 1559-7016
Keywords: Ischaemic stroke, ischaemic penumbra, proteomics, animal models, cerebral infarction
Copyright Information: © The Author(s) 2024. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International Licence.
Funders: National Health and Medical Research Council (NHMRC)
Date Deposited: 01 May 2024 03:51
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 > 200105 Treatment of human diseases and conditions @ 100%
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