Abstract
Neural stem cells (NSCs) transplantation is one of the most promising strategies for the treatment of CA-induced brain damage. The transplanted NSCs could differentiate into new neuron and replace the damaged one. However, the poor survival of NSCs in severe hypoxic condition is the limiting step to make the best use of this kind of therapy. In the present study, we investigated whether the overexpression of miR-26a improves the survival of NSCs in hypoxic environment in vitro and in vivo. In vitro hypoxia injury model is established in NSCs by CoCl2 treatment, and in vivo cardiac arrest (CA) model is established in Sprague-Dawley (SD) rats. Quantitative real-time polymerase chain reaction is used to detect the mRNA level and Western blot is used to examine the protein level of indicated genes. TUNEL staining and flow cytometry are applied to evaluate apoptosis. Dual-luciferase reporter assay is utilized to analyze the target gene of miR-26a. The expression of miR-26a is reduced in both in vitro and in vivo hypoxic model. MiR-26a directly targets 3′-UTR of glycogen synthase kinase 3β (GSK-3β), resulting in increased β-catenin expression and decreased apoptosis of NSCs. Overexpression of miR-26a in transplanted NSCs improves the survival of NSCs and neurological function in CA rats. MiR-26a prevents NSCs from apoptosis by activating β-catenin signaling pathway in CA-induced brain damage model. Modulating miR-26a expression could be a potential strategy to attenuate brain damage induced by CA.
Highlights
Cardiac arrest is an immense and sustained public health problem and more than 500,000 patients die from a cardiac arrest each year [1]
In order to examine whether miR-26a is associated with the neural stem cell (NSC) damage in hypoxic condition, we performed Quantitative real-time polymerase chain reaction (qRT-PCR) to detect the relative mRNA levels of miR-26a in both hypoxia injury model and cardiac arrest (CA) model
The reduced expression of miR-26a in hypoxic condition indicates miR-26a may play a pivotal role in CA-mediated brain damage and modulating apoptosis of NSCs in low oxygen environment
Summary
Cardiac arrest is an immense and sustained public health problem and more than 500,000 patients die from a cardiac arrest each year [1]. It induces the cessation of cerebral blood flow, which can result in brain damage. It is well established that neural stem cells (NSCs) are essential for regeneration of the nervous system, which secrete various neurotrophic factors and cytokines to improve microenvironment and maintain blood–brain barrier integrity, or differentiate into different cell types to compensate for hypoxia-induced cell death, strengthen the synapses connection, and establish new neural circuits to reduce hypoxic brain injury and ameliorate neurobehavioral recovery [3,4,5,6]. NSCs that are exposed to such hypoxic environment undergo apoptosis, which is License 4.0 (CC BY)
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