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CORM-3 Regulates Microglia Activity, Prevents Neuronal Injury, and Improves Memory Function During Radiation-induced Brain Injury

[ Vol. 17 , Issue. 4 ]

Author(s):

Kui Lu*, Wen-Jun Wu, Cheng Zhang, Yu-Liang Zhu, Jian-Qiang Zhong and Jie Li   Pages 464 - 470 ( 7 )

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.

Keywords:

Microglia cells, radiation brain injury, inflammation, carbon monoxide, nerve regeneration, brain parenchyma.

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



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