Pre-Ischemic Oxytocin Treatment Alleviated Neuronal Injury via Suppressing NF-κB, MMP-9, and Apoptosis Regulator Proteins in A Mice Model of Stroke

Abstract

Objective: This study was designed to determine the effects of pre-ischemic administration of oxytocin (OXT) on neuronal injury and possible molecular mechanisms in a mice model of stroke. Materials and Methods: In this experimental study, stroke was induced in the mice by middle cerebral artery occlusion (MCAO) for 60 minutes and 24 hours of reperfusion. OXT was given as intranasal daily for 7 consecutive days before ischemic stroke. Neuronal damage, spatial memory, and the expression levels of nuclear factor-kappa B (NF-κB), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), brain-derived neurotrophic factor (BDNF) and apoptosis were assessed 24 hours after stroke. Results: Pre-ischemic treatment with OXT significantly reduced the infarct size (P<0.01); but did not recover the neurological and spatial memory dysfunction (P>0.05). Moreover, OXT treatment considerably decreased the expressions of NF-κB, TNF-α, IL-1β, and MMP-9 (P<0.001) and enhanced the level of BDNF protein. OXT treatment also significantly downregulated Bax expression and overexpressed Bcl-2 proteins. Conclusion:The finding of this study indicated that administration of OXT before ischemia could limit brain injury by inhibiting MMP-9 expression, apoptosis, inflammatory signaling pathways, and an increase in the BDNF protein level. We suggested that OXT may be potentially useful in the prevention and/or reducing the risk of the cerebral stroke attack, and could be offered as a new prevention option in the clinics.