Downregulating EVA1C exerts the potential to promote neuron growth after neonatal hypoxic-ischemic encephalopathy injury associated with alternative splicing.

Neonatal hypoxic-ischemic encephalopathy (NHIE) is one of the major diseases in newborns during the perinatal stage, which globally is the main reason for children's morbidity and mortality. However, the mechanism of NHIE still remains poorly clear. In this study, the 7-day-old rats were subjected to hypoxic-ischemia (HI), then brain damage was detected. Afterward, the expression of eva-1 homolog C (EVA1C) was measured in vitro by establishing the oxygen-glucose deprivation (OGD) model in SHSY5Y cells and human fetal neurons. Subsequently, the potential function and mechanism of EVA1C were explored by silencing EVA1C and alternative splicing prediction. As a result, obvious neurobehavioral impairment and brain infarction were detected through Zea-Longa score and TTC staining; meanwhile, neuron injury was tested by HE and Nissl staining post HI. Moreover, it was found that the expression of EVA1C was notably upregulated in SHSY5Y cells and human fetal neurons after OGD. In addition, cell survival and growth were increased after silencing EVA1C, which might be associated with alternative splicing. In conclusion, EVA1C interference exhibited potential in promoting neuron survival and growth, associated with exon skipping with the alternative splicing site in 34613318:34687258, which may provide the basis for the therapeutic target and mechanism research of NHIE.