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

Author(s): Kui Lu*, Wen-Jun Wu, Cheng Zhang, Yu-Liang Zhu, Jian-Qiang Zhong, Jie Li

Journal Name: Current Neurovascular Research

Volume 17 , Issue 4 , 2020

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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.

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Article Details

VOLUME: 17
ISSUE: 4
Year: 2020
Published on: 14 December, 2020
Page: [464 - 470]
Pages: 7
DOI: 10.2174/1567202617999200730213259
Price: $65

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