Carbon Monoxide Releasing Molecule-3 (CORM-3) Regulates Microglia Activity, Prevents Neuronal Injury, and Improves Memory Function Dur-ing Radiation Induced Brain Injury.

OBJECTIVES This study aims to explore in detail the mechanism of the carbon monoxide releasing molecule-3 (CORM-3) in regulating the activity of microglia (MG) in the treatment of radiation brain injury (RBI). METHODS The brain injury models of BV2 cells and Balb/C mice were established and randomly divided into three groups: the normal control group (CON), the single radiation group (RAD), and the radiation plus CORM-3 intervention group (RAD+CORM). Immunofluorescence was used to observe the effects on activation of the MG. The expressions of inflam-matory factors, such as intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS), were detected by Western blot. Neuron apoptosis and regeneration in the radiation brain injury (RBI)model were detected by neuronal nuclear antigen (NeuN)+TUNEL and NeuN+BrdU double staining. A Morris water maze was used to assess the spa-tial learning and memory of the mice. RESULTS Within 48 hours after radiation, CORM-3 inhibited activation of the MG, blocked the phosphorylation of P38, and increased the expression of ICAM-1 and iNOS. Therefore, CORM-3 might alleviate MG-mediated neuronal apoptosis and promote neuralregeneration in the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. CORM-3 could in-crease the swimming distance and platform-stay time of the mice in the target platform quadrant after radiation. CONCLUSION CORM-3 could effectively improve the inflammatory response induced by activation of the MG, reduce neu-ronal apoptosis, promote neural regeneration, and improve the learning and memory performance of mice after radiation.