Department of Neurology, Zhongshan City People's Hospital, Zhongshan, Guangdong 528403, China.
Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Curr Neurovasc Res. 2020;17(4):464-470. doi: 10.2174/1567202617999200730213259.
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).
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.
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.
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.
本研究旨在详细探讨一氧化碳释放分子-3（CORM-3）在调节辐射性脑损伤（RBI）中小胶质细胞（MG）活性中的作用机制。
建立 BV2 细胞和 Balb/C 小鼠脑损伤模型，并随机分为三组：正常对照组（CON）、单纯照射组（RAD）和照射加 CORM-3 干预组（RAD+CORM）。免疫荧光法观察 MG 活化的影响。Western blot 检测细胞间黏附分子-1（ICAM-1）和诱导型一氧化氮合酶（iNOS）等炎症因子的表达。通过神经元核抗原（NeuN）+TUNEL 和 NeuN+BrdU 双重染色检测辐射性脑损伤（RBI）模型中神经元的凋亡和再生。Morris 水迷宫评估小鼠的空间学习和记忆能力。
照射后 48 h 内，CORM-3 抑制 MG 的活化，阻断 P38 的磷酸化，增加 ICAM-1 和 iNOS 的表达。因此，CORM-3 可能通过减轻 MG 介导的神经元凋亡并促进海马齿状回颗粒下区（SGZ）的神经再生，从而缓解辐射引起的炎症反应。CORM-3 可增加照射后小鼠在目标平台象限中的游泳距离和平台停留时间。
CORM-3 可有效改善 MG 活化引起的炎症反应，减少神经元凋亡，促进神经再生，改善小鼠的学习和记忆能力。
