Objective: 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 inflammatory 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 spatial learning and memory of the mice.
Results: Within 48 h 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 neural regeneration in the subgranular
zone (SGZ) of the dentate gyrus of the hippocampus. CORM-3 could increase 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 neuronal apoptosis, promote neural regeneration, and improve the learning and
memory performance of mice after radiation.