Introduction: Nucleobinding-2 (NUCB2) or nesfatin-1, a newly identified anorexigenic peptide, has antioxidant, anti-inflammatory, and anti-apoptotic properties. Brain ischemiareperfusion induces irreversible damages, especially in the hippocampus area. However, the therapeutic effects of NUCB2 have not been well investigated in cerebral ischemia. This study was designed for the first time to investigate the protective effects of NUCB2/Nesfatin-1 on the expression of apoptosis-related proteins and reactive astrogliosis level in the CA1 area of hippocampus in an experimental model of transient global cerebral ischemia. Methods: The male Wistar rats were randomly allocated into 4 groups (sham, NUCB2, ischemia-reperfusion, and ischemia-reperfusion+NUCB21) (n =7). The model of cerebral ischemia was prepared by common carotid arteries occlusion for 20 minutes. Nesfatin-1 (20 μg/kg) and saline (as a vehicle) were injected (intraperitoneally) at the beginning of the reperfusion period. The assessment of the protein expression levels was performed by immunofluorescence and immunohistochemical staining. Results: NUCB2 significantly reduced the Bax and GFAP protein levels in the CA1 area after ischemia (P<0.05). Also, NUCB2 increased Bcl-2 protein level (P<0.05). NUCB2 exerted protective effects against ischemic injury by the inhibition of astrocytes activation as an inflammatory response and decreased neuronal cell apoptosis. Conclusion: The present study provides the possible neuroprotective view of nesfatin-1 in the treatment of ischemia injury model in rat hippocampus.

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