Effects of Inhibition of miR-155-5p in Neural Stem Cell Subarachnoid Transplant on Rats with Cerebral Infarction.

Abstract

Cerebral infarction is a leading cause of death, which calls for effective prevention and treatment. Transplant of neural stem cells (NSCs) is a potential therapeutic treatment to cerebral infarction although its efficacy still needs to be improved. Overexpression of hypoxia-inducible factor 1α (HIF-1α) has been shown to enhance the protective effects of stem cell transplant on cerebral infarction. The expression of HIF-1α is predicted to be regulated by miR-155-5p. Therefore, we regulated the expression of miR-155-5p in NSCs and evaluated the effects of miR-155-5p-regulated NSC transplant on cerebral infarction. We inhibited miR-155-5p expression in NSCs by overexpressing miR-155-5p inhibitor. HIF-1α expression, cell viability, and the expression of apoptosis markers were examined. We established the middle cerebral artery occlusion (MCAO) rat model, and the infarct volume, neurobehavioral outcomes, inflammation, and oxidative stress were evaluated after NSC transplant. miR-155-5p directly targeted HIF-1α and negatively regulated its expression. Inhibition of miR-155-5p enhanced cell viability and prevented cell apoptosis. Transplant of miR-155-5p-inhibited NSCs significantly decreased infarct volume and improved neurobehavioral outcomes of MCAO rats. Transplant of miR-155-5p-inhibited NSCs significantly inhibited inflammation and oxidative stress. Inhibition of miR-155-5p in NSCs resulted in enhanced protection against cerebral infarction after NSC transplant.