Oxytocin improves ischemic stroke by reducing expression of excitatory amino acid transporter 3 in rat MCAO model

J Immunoassay Immunochem. 2021 Sep 3;42(5):513-524. doi: 10.1080/15321819.2021.1906270. Epub 2021 Mar 31.

Abstract

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 (P< .05). In addition, OT reduces the number of neurons with pyknotic nuclei that are significantly increased in the ischemic region (P< .01) Immunohistochemistry results showed that although EAAT3 expression increased after ischemia, OT therapy increased EAAT3 expression further (P< .05). Therefore, increased EAAT3 expression could be one of the neuroprotective mechanisms of OT after MCAO.

Keywords: EAAT3; Ischemic stroke; MCAO; oxytocin.

MeSH terms

  • Animals
  • Brain Ischemia* / drug therapy
  • Disease Models, Animal
  • Excitatory Amino Acid Transporter 3
  • Glutamates
  • Infarction, Middle Cerebral Artery / drug therapy
  • Ischemic Stroke*
  • Male
  • Oxytocin / pharmacology
  • Rats
  • Stroke* / drug therapy

Substances

  • Excitatory Amino Acid Transporter 3
  • Glutamates
  • Oxytocin