MicroRNA-410 inhibition of the TIMP2-dependent MAPK pathway confers neuroprotection against oxidative stress-induced apoptosis after ischemic stroke in mice

•Effects of miR-410 on ischemic stroke via TIMP2-dependent MAPK pathway.•Ischemic stroke tissues exhibited downregulated miR-410 and upregulated TIMP2.•TIMP2 is a target gene of miR-410.•Increased miR-410/decreased TIMP2 promotes cell survival rate & inhibits apoptosis.•The study builds a theoretical basis for new therapeutic targets of ischemic stroke. Ischemic stroke (IS) is an acute cerebral event characterized by a high incidence rate, high disability rate as well as a high mortality. More recently, accumulative literature has provided evidence highlighting the role played by microRNAs (miRs) in the development of neurons. Hence, the aim of the present study was to investigate the neuroprotective role of miR-410 in IS. Microarray-based gene expression profiling of AMI was conducted in order to identify differentially expressed genes (DEGs) and the corresponding miRs regulating these genes. IS models were established to assess neurology on a scoring basis. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) were all subsequently assessed. The functional role of miR-410 in IS was determined based on ectopic expression, knockdown and reporter assay experiments in hippocampal neurons. The expressions of microRNA-410, TIMP2, ERK, p38MAPK, JNK were all examined accordingly. The survival rate was assessed by MTT assay, and cell cycle and apoptosis by flow cytometry. After the loss of hippocampal neurons, infarct size as well as oxidative stress injury had been detected, microarray technology revealed that TIMP2 was differentially expressed in IS and that miR-410 regulated TIMP2. Initial observations revealed elevated levels of TIMP2 expression and MDA activity, in addition to evidence obtained indicated that the MAPK pathway had been activated along with decreased SOD, GSH-Px activity and miR-410 expression in IS mice. Ectopic expression of miR-410 was observed to inactivate the MAPK pathway, TIMP2 expression and hippocampal neuron apoptosis, while elevated hippocampal neuron survival rates and cell cycle entry were detected. Furthermore, TIMP2 as a direct target gene of miR-410, was determined to be negatively regulated by miR-410, while the MAPK pathway was found to be inhibited following TIMP2 knockdown. Our results revealed that the overexpression of miR-410 could ameliorate hippocampal neuron loss, reduce infarct size and oxidative stress injury in IS mice. Taken together, the key evidence of the current study e