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dc.contributor.authorLiu, Ye-
dc.contributor.authorEaton, Emma D-
dc.contributor.authorWills, Taryn E-
dc.contributor.authorMcCann, Sarah K-
dc.contributor.authorAntonic, Ana-
dc.contributor.authorHowells, David W-
dc.identifier.citationTranslational stroke research 2018; online first: 23 March-
dc.description.abstractLow 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 H2O2injury (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 H2O2injury 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.-
dc.subjectHuman ischaemic cascade-
dc.subjectIn vitro ischaemia-related injuries-
dc.subjectSH-SY5Y cells-
dc.subjectStudy quality-
dc.subjectSystematic review and meta-analysis-
dc.titleHuman Ischaemic Cascade Studies Using SH-SY5Y Cells: a Systematic Review and Meta-Analysis.-
dc.typeJournal Article-
dc.identifier.journaltitleTranslational stroke research-
dc.identifier.affiliationThe Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia-
dc.identifier.affiliationSchool of Medicine, Faculty of Health, University of Tasmania, Medical Sciences Precinct, Hobart, TAS, Australia-
dc.identifier.affiliationThe Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia-
dc.identifier.affiliationCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, EH16 4SB, UK-
dc.identifier.affiliationDepartment of Neuroscience, Monash University, Melbourne, VIC, 3004, Australia-
dc.type.austinJournal Article-
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
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