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Human ischaemic cascade studies using SH-SY5Y cells: a systematic review and meta-analysis


Liu, Y and Eaton, ED and Wills, TE and McCann, SK and Antonic, A and Howells, DW, Human ischaemic cascade studies using SH-SY5Y cells: a systematic review and meta-analysis, Translational Stroke Research, 9, (6) pp. 564-574. ISSN 1868-4483 (2018) [Refereed Article]


Copyright Statement

Copyright 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1007/s12975-018-0620-4


Low translational yield for stroke may reflect the focus of discovery science on rodents rather than humans. Just how little is known about human neuronal ischaemic responses is confirmed by systematic review and meta-analysis revealing that data for the most commonly used SH-SY5Y human cells comprises only 84 papers. Oxygen-glucose deprivation, H2O2, hypoxia, glucose-deprivation and glutamate excitotoxicity yielded − 58, − 61, − 29, − 45 and − 49% injury, respectively, with a dose-response relationship found only for H2O2 injury (R2 = 29.29%, p < 0.002). Heterogeneity (I2 = 99.36%, df = 132, p < 0.0001) was largely attributable to the methods used to detect injury (R2 = 44.77%, p < 0.000) with cell death assays detecting greater injury than survival assays (− 71 vs − 47%, R2 = 28.64%, p < 0.000). Seventy-four percent of publications provided no description of differentiation status, but in the 26% that did, undifferentiated cells were susceptible to greater injury (R2 = 4.13%, p < 0.047). One hundred and sixty-nine interventions improved average survival by 34.67% (p < 0.0001). Eighty-eight comparisons using oxygen-glucose deprivation found both benefit and harm, but studies using glutamate and H2O2 injury reported only improvement. In studies using glucose deprivation, intervention generally worsened outcome. There was insufficient data to rank individual interventions, but of the studies reporting greatest improvement (> 90% effect size), 7/13 were of herbal medicine constituents (24.85% of the intervention dataset). We conclude that surprisingly little is known of the human neuronal response to ischaemic injury, and that the large impact of methodology on outcome indicates that further model validation is required. Lack of evidence for randomisation, blinding or power analysis suggests that the intervention data is at substantial risk of bias.

Item Details

Item Type:Refereed Article
Keywords:human ischaemic cascade, SH-SY5Y cells, systematic review and meta-analysis, in vitro ischaemia-related injuries, study quality
Research Division:Biomedical and Clinical Sciences
Research Group:Cardiovascular medicine and haematology
Research Field:Cardiology (incl. cardiovascular diseases)
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Eaton, ED (Dr Emma Eaton)
UTAS Author:Howells, DW (Professor David Howells)
ID Code:131302
Year Published:2018
Web of Science® Times Cited:13
Deposited By:Medicine
Deposited On:2019-03-12
Last Modified:2019-05-13
Downloads:19 View Download Statistics

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