Introduction: Brain injury induces an almost immediate response from glial cells, especially astrocytes. In fact, activation of astrocytes leads to production of inflammatory cytokines and reactive oxygen species that may result in secondary neuronal damage. Melatonin is an anti-inflammatory and antioxidant agent, and it has been reported to exert neuroprotection through prevention of neuronaldeath in several models of central nervous system injury.In this study, we aimed to investigate the effect of melatonin on astrocyte activation induced by traumatic brain injury (TBI) in rat hippocampus and dentate gyrus.

Methods: Animals were randomly divided into 5 groups; Sham group, TBI group, vehicle group and melatonin‐treated TBI groups (TBI+Mel5, TBI+Mel20). Immunohistochemical method (GFAP marker)and TUNEL assay was used to evaluate astrocyte reactivity and neuronal death, respectively.

Results: The results demonstrated that, the number of astrocyte was reduced significantly in melatonin‐treated groups compared to the vehicle group. Additionally, based on TUNEL results, melatonin administration noticeably reduced the number of apoptotic neurons in rat hippocampus and dentate gyrus.

Conclusion: In general, our findings suggest that melatonin treatment afterbrain injury reduces astrocyte reactivity as well as neuronal cells apoptosis in rat hippocampus and dentate gyrus.