Title:CORM-3 Regulates Microglia Activity, Prevents Neuronal Injury, and Improves Memory Function During Radiation-induced Brain Injury
VOLUME: 17 ISSUE: 4
Author(s):Kui Lu*, Wen-Jun Wu, Cheng Zhang, Yu-Liang Zhu, Jian-Qiang Zhong and Jie Li
Affiliation:Department of Neurology, Zhongshan City People's Hospital, Zhongshan, Guangdong 528403, Department of Neurology, Zhongshan City People's Hospital, Zhongshan, Guangdong 528403, Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, Department of Radiation Oncology, Zhongshan City People's Hospital, Zhongshan, Guangdong 528403, Department of Neurology, Zengcheng District People's Hospital of Guangzhou, Guangdong 511300, Department of Neurology, Zengcheng District People's Hospital of Guangzhou, Guangdong 511300
Keywords:Microglia cells, radiation brain injury, inflammation, carbon monoxide, nerve regeneration, brain parenchyma.
Abstract:
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.
