Human Ischaemic Cascade Studies Using SH-SY5Y Cells: a Systematic Review and Meta-Analysis

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 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 o...
Source: Translational Stroke Research - Category: Neurology Source Type: research