Objective The expression cold-inducible RNA-binding protein (CIRP) is significantly enhanced in neurons under hypothermia,but its roles remain unclear.This study aims to investigate whether the cerebral protection under hypothermia is mediated by the CIRP-mediated inhibition of neuronal apoptosis.Methods Primary rat cortical neurons were isolated,cultured,and transduced with lentiviral CIRP-RNAi.Apoptosis of the transduced neurons was induced with 100 μmol/L H2O2.The treated cells were divided into two groups,and cultured in 37℃ or 32℃ incubator respectively.Cell viability was detected by MTT colorimetric assay.Neuronal apoptosis was detected by flow cytometry after labeling the cells with Hoechst 33342 and Annexin V-FITC/PI.The protein expressions of CIRP,activated Caspase-3,and thioredoxin (TRX) were detected by Western blot.Results Under 32℃,CIRP protein was significantly induced in cortical neurons; the expression of activated Caspase-3 was decreased,while the TRX expression was increased.The rate of neuronal apoptosis was (4.5 ± 0.8) %.Under 37 ℃,CIRP expression was evidently reduced in cortical neurons; the expression of activated caspase-3 was significantly enhanced,and TRX expression was reduced.The rate of neuronal apoptosis reaches (53.5 ± 1.7) % (P< 0.05,compared to that in 32 ℃ group).Conclusions The induction of CIRP protein in rat cortical neurons under hypothermia inhibits H2O2-induced neuronal apoptosis and thereby exerts neuroprotective effect,which forms one of the cerebral protective pathways under hypothermia. Key words: Cold-inducible RNA-binding protein; Neurons; Cerebral cortex ; Apoptosis; Hypothermia