oxytocin and Ischemic-Stroke

Various molecular mechanisms are activated in neurons during ischemic stroke. Extracellular glutamate secretion into brain tissue causes neurotoxicity and brain damage. Excitatory amino acid transporter 3 (EAAT3) could remove the extracellular glutamate. Neuroprotective activity of oxytocin (OT) in ischemia of various tissues has been reported. This study investigates the neuroprotective effect of OT in an animal model of middle cerebral artery occlusion (MCAO) and the possible role of EAAT3. Transient MCAO was performed as a model of ischemic stroke in male rats and then OT was administrated intra-nasally. Infarct volume was measured by 2, 3, 5-triphenyl tetrazolium chloride staining. Nissl staining method was performed for the evaluation of neuronal cell morphology. Immunohistochemistry assay was performed to analyze the EAAT3 expression in the ischemic region. OT significantly reduced the infarct volume in the cerebral cortex and striatum after ischemia (

Topics: Animals; Brain Ischemia; Disease Models, Animal; Excitatory Amino Acid Transporter 3; Glutamates; Infarction, Middle Cerebral Artery; Ischemic Stroke; Male; Oxytocin; Rats; Stroke

The present study was designed to determine the effect of different doses of oxytocin (OXT) on neuronal injury, spatial memory, blood-brain barrier (BBB) integrity and to explore possible underlying molecular mechanisms in the early stage of stroke in mice. Stroke model was generated by middle cerebral artery occlusion (MCAO) for 60 min and 24 h reperfusion in mice. OXT at doses of 1, 2, 4 and 8 IU/per mouse was administrated intranasally at the beginning of brain ischemia. Brain injury, BBB integrity, and spatial memory were evaluated by standard methods. Changes in the expression of nuclear factor-kappa B (NF-κB), and TUNEL positive cell were detected by immunohistochemistry. The levels of vascular endothelial growth factor (VEGF), aquaporin-4 (AQP4) and brain-derived neurotrophic factor (BDNF) proteins were determined by western blotting and ELISA methods. OXT at doses of 4 and 8 IU/per mouse reduced the infarct size by 42% and 52%, respectively, and improved spatial memory function (p < 0.001). OXT (8 IU/per mouse) significantly reduced brain edema, BBB disruption and upregulated the AQP4 expression (p < 0.001). Finally, OXT significantly diminished the number of apoptotic, NF-κB positive cells and enhanced the expression of BDNF and VEGF proteins in the brain tissue (p < 0.001). These findings provide important evidences that OXT significantly suppresses neuronal damage in the early stage of stroke by inhibiting apoptotic and NF-κB signaling pathway, increasing the expression of VEGF, AQP4 and BDNF proteins and reducing the BBB leakage.

Topics: Animals; Aquaporin 4; Blood-Brain Barrier; Brain Edema; Brain-Derived Neurotrophic Factor; Cerebral Infarction; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery; Ischemic Stroke; Male; Mice; Nerve Tissue Proteins; NF-kappa B; Oxytocin; Signal Transduction; Single-Blind Method; Spatial Memory; Vascular Endothelial Growth Factor A