Obesity is a predominant risk factor in ischemic stroke and is commonly comorbid with it. Pathologies following these conditions are associated with systemic and local inflammation. Moreover, there is increasing evidence that the susceptibility for ischemic brain damage increases substantially in experimental models of ischemic stroke with concomitant obesity. Herein, we explore the proinflammatory events that occur during ischemic stroke and obesity, and we discuss the influence of obesity on the inflammatory response and cerebral damage outcomes in experimental models of brain ischemia. In addition, because melatonin is a neurohormone widely reported to exhibit protective effects in various diseases, this study also demonstrates the anti‐inflammatory role and possible mechanistic actions of melatonin in both epidemic diseases. A summary of research findings suggests that melatonin administration has great potential to exert an anti‐inflammatory role and provide protection against obesity and ischemic stroke conditions. However, the efficacy of this hormonal treatment on ischemic stroke with concomitant obesity, when more serious inflammation is generated, is still lacking.
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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