The RNA-binding proteins promote resistance of microglial cells to hypoxia

Purpose: Microglial cells play a crucial role in responding to brain hypoxia. This study aimed to evaluate the effect of RNA-binding proteins (RBPs) on the resistance of microglial cells to hypoxia. Methods: Newborn rats were subjected to hypoxia under four conditions: hypoxia (H), one week after hypoxia induction (H1), control (C), and control one week after hypoxia induction (C1). Microglial cells were isolated and cultured, and exosomes were extracted from brain samples of healthy newborn rats of C1 group. RBPs were extracted from the aforementioned groups and transferred into the microglial cells using exosomes from the C1 group. Cell viability, expression of specific RBP genes, and innate immune factors were evaluated in the studied groups. Additionally, exosomes containing RBPs were injected into the hypoxic rats to investigate behavioral changes in-vivo. Results: The treatment of microglial cells with C1 exosomes elevated the viability rate. The RBP-H proteins significantly elevated the expression of the CPE, HIF-1α, PDI, and VEGF-A genes. Improvements in anti-protease activity, along with decreases in lysozyme and myeloperoxidase activity, were observed in hypoxic microglial cells following treatment with RBP-H and exosomes containing RBP-H. In vivo evaluations revealed that the hypoxic group treated with exosome loading with RBP-H exhibited significant improvements in recognition and balance maintenance. Conclusion: The RBPs may be considered a promising option for further studies in the treatment of brain disorders resulting from hypoxia.