Human Umbilical Cord Mesenchymal Stem Cells Efficiently Improve Neurobehavioral Status and Alleviate Brain Injury in Hypoxia/Ischemia-Induced Cerebral Palsy Rat Model Via Down-Regulating the Nogoa/Ngr/Rho Pathway

Abstract

Background: Cerebral palsy (CP) is a brain injury disease, which is a global public health issue with an estimated prevalence of 2‰—4‰ and imposes a substantial health burden on many countries. At present, there is no ideal treatment available and most of them will still suffer adverse outcomes. Human umbilical cord mesenchymal stem cells(HUCMSCs) application in many fields of medicine, which can promote nervous system regeneration and inhibit neuroinflammation. The regeneration of central nervous system(CNS) is related to the nervous regeneration inhibitors. NogoA/NgR/Rho pathway is very important to the nerve growth, CP injury is inevitably accompanied by the regeneration and repair of neurons and axons. so we hypothesized that NogoA/NgR/Rho pathway is involved in when using the HUCMSCs to treatment cerebral palsy.Purpose: In this study, we might clarify the NogoA/NgR/Rho pathway functional role in mediating HUCMSCs to improve neurobehavioral status and alleviate brain injury in hypoxia/ischemia-induced CP rat model.Methods: The CP rat model was established by ligating the left common carotid artery and anoxia for 2.5 h, and HUCMSCs were intravenous injected to the modeled rats. The neurobehavioral situation and brain pathological injury in CP rats were determined via a series of assays. The mRNA and protein expression of NogoA、NgR、RhoA、Rac-1、Cdc42 in brain tissue of rats in each group was detected by RT-qPCR and western blot analysis. Results: The CP rats exhibited obvious motor function abnormalities, pathological damage and a lot of brain nerve cell apoptosis. Compared with CP+PBS group and CP group rats, HUCMSCs transplantation can significantly improve the neurobehavioral situation, attenuated brain pathological injury, inhibit apoptosis of brain nerve cells and the activation of astrocytes in CP rats. The expression of NogoA、NgR、RhoA relative mRNA and protein in brain tissues of rats in the CP+PBS group and CP group rats were significantly lower than those of in the sham+PBS and CP+HUCMSCs group. The expression of Rac-1、Cdc42 relative mRNA and protein in brain tissues of rats in the sham and CP+HUCMSCs group was significantly higher than those of in CP+PBS group and CP group rats. Conclusion: This study confirmed that HUCMSCs can efficiently improve neurobehavioral status and alleviate brain injury in hypoxia/ischemia-induced cerebral palsy rat model via down-regulating the NogoA/NgR/Rho pathway.