星形胶质增生
褪黑素
神经保护
胶质瘢痕
星形胶质细胞
葛兰素史克-3
再灌注损伤
缺血
医学
药理学
胶质纤维酸性蛋白
内分泌学
内科学
生物
激酶
中枢神经系统
细胞生物学
免疫组织化学
作者
Nuttapong Yawoot,Jirakhamon Sengking,Piyawadee Wicha,Piyarat Govitrapong,Chainarong Tocharus,Jiraporn Tocharus
摘要
Even though astrocytes have been widely reported to support several brain functions, studies have emerged that they exert deleterious effects on the brain after ischemia and reperfusion (I/R) injury. The present study investigated the neuroprotective effects of melatonin on the processes of reactive astrogliosis and glial scar formation, as well as axonal regeneration after transient middle cerebral artery occlusion. Male Wistar rats were randomly divided into four groups: sham-operated, I/R, I/R treated with melatonin, and I/R treated with edaravone. All drugs were administered via intraperitoneal injection at the onset of reperfusion and were continued until the rats were sacrificed on Day 7 or 14 after the surgery. Melatonin presented long-term benefits on cerebral damage after I/R injury, as demonstrated by a decreased infarct volume, histopathological changes, and reduced neuronal cell death. We also found that melatonin attenuated reactive astrogliosis and glial scar formation and, consequently, enhanced axonal regeneration and promoted neurobehavioral recovery. Furthermore, glycogen synthase kinase-3 beta (GSK-3β) and receptor-interacting serine/threonine-protein 1 kinase (RIP1K), which had previously been revealed as proteins involved in astrocyte responses, were significantly reduced after melatonin administration. Taken together, melatonin effectively counteracted the deleterious effects due to astrocyte responses and improved axonal regeneration to promote functional recovery during the chronic phase of cerebral I/R injury by inhibiting GSK-3β and RIP1K activities.
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