Abstract
Ischemic stroke is a common cerebrovascular disease and recovering blood flow as early as possible is essential to reduce ischemic damage and maintain neuronal viability, but the reperfusion process usually causes additional damage to the brain tissue in the ischemic area, namely ischemia reperfusion injury. The accumulated studies have revealed that transplantation of exogenous neural stem cells (NSCs) is an ideal choice for the treatment of ischemia reperfusion injury. At present, the source and efficacy of exogenous NSCs after transplantation is still one of the key issues that need to be resolved. In this study, human umbilical cord mesenchymal stem cells (hUC-MSCs) were obtained and induced into NSCs byadding growth factor and neuregulin1β (NRG1β) was introduced during the differentiation process of NSCs. Then, the rat middle cerebral artery occlusion/reperfusion (MCAO/R) models were established, and the therapeutic effects were evaluated among groups treated by NRG1β, NSCs and NSCs pretreated with 10 nM NRG1β (NSCs-10 nM NRG1β) achieved through intra-arterial injection. Our data show that the NSCs-10 nM NRG1β group significantly improves neurobehavioral function and infarct volume after MCAO/R, as well as cerebral cortical neuron injury, ferroptosis-related indexes and mitochondrial injury. Additionally, NSCs-10 nM NRG1β intervention may function through regulating the p53/GPX4/SLC7A11 pathway, and reducing the level of ferroptosis in cells, further enhance the neuroprotective effect on injured cells.
Highlights
Ischemic stroke is the second most common cause of death and disability in the world, and with the aging of the world’s population, the incidence of which is increasing year by year [1]
The fluorescence intensity analysis results showed that the fluorescence intensity of SOX2 and Nestin increased significantly in the 10 nM NRG1β group compared with the control group (Figure 1c, p < 0.01, p < 0.05)
In order to investigate the effects of neural stem cells (NSCs) pretreated with 10 nM NRG1β transplantation on behavioral dysfunction caused by middle cerebral artery occlusion/reperfusion (MCAO/R), the behavioral tests were performed with the modified neurological severity score (mNSS) method on day
Summary
Ischemic stroke is the second most common cause of death and disability in the world, and with the aging of the world’s population, the incidence of which is increasing year by year [1]. It has been reported that ischemic stroke is a phenomenon in which the lack of blood supply in the brain leads to the insufficient supply of oxygen and glucose for the survival of neurons, changing the microenvironmental homeostasis of neurons and leading to cell death [2]. Due to the harmful effects of the ischemia microenvironment and the limited regeneration ability of endogenous neural cells, many ischemic stroke patients lack an appropriate immune microenvironment as well as enough nerve cells to complement and repair damaged brain tissue, and eventually produce a permanent partial loss of nerve tissue and brain nerve function defect after regional blood flow restoration [8]. Along with the development of stem cells research, disease therapy using stem cells, especially neural stem cells (NSCs), has attracted more and more attention, which provides novel insights for the treatment of neurological diseases including ischemic stroke in the future in clinical
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