Prophylactic effect of intranasal oxytocin on brain damage and neurological disorders in global cerebral ischemia in mice

OBJECTIVE(S): A few experimental studies have shown the therapeutic effects of oxytocin on focal cerebral ischemia. In this study, the prophylactic effect of intranasal oxytocin on brain damage was investigated in a cerebral ischemic model. MATERIALS AND METHODS: Intranasal oxytocin (8 IU/per mouse) was prescribed daily for one week. Cerebral ischemia was performed through bilateral common carotid artery occlusion (BCCAO) for 20 min and then blood flow was restored for 24 hr. Finally, neurological disorders, spatial learning and memory, neuronal death, and neuronal apoptosis were assessed in CA1, CA3, and dentate gyrus. Also, levels of interleukin-1β (IL-1β) and Tumor necrosis factor-alpha (TNFα) were measured in the hippocampus. RESULTS: Induction of global ischemia leads to neurological disorders and impairment of spatial learning and memory that are improved by pre-treatment with oxytocin (P<0.01). Cresyl violet staining showed that pretreatment with oxytocin significantly reduced the number of dead nerve cells in CA1, CA3, and dentate gyrus by 40.7, 32, and 34.3%, respectively. Also, positive TUNEL cells in CA1, CA3, and dental gyrus decreased by 15, 30, and 27%, respectively. In addition, levels of TNFα and IL-1β, which were extensively increased in ischemic mice, were significantly reduced with oxytocin pre-treatment. CONCLUSION: Pre-treatment of oxytocin reduces ischemic damage and improves neurological function and spatial memory. The neuroprotective effect of oxytocin is mediated by a decrease in cell death, apoptosis, and inflammatory mediators TNFα and IL-1β. Pre-treatment with oxytocin may be useful in people who are prone to stroke.