Evaluating the Effect of Estrogen and Progesterone on Expression of EAAT2 and EAAT3 Glutamate Transporters Following Focal Cerebral Ischemia in Rats

Abstract

Abstract Background: Glutamate is the most widespread excitatory neurotransmitter in the mammalian central nervous system (CNS) and plays major role in the pathogenesis of ischemia brain injury.Glutamate transporters have a major role in glutamate removal and maintain its concentration below excitotoxic levels. Although estrogen’s and progesterone’s neuroprotective effects were well-described, the exact molecular mechanism has yet to be determined. This study has investigated estrogen and progesterone effect on glutamate transporters expression in the ischemic penumbra/peri-infarct region in rat. Materials and Methods: Adult male Wistar rats were subjected to transient middle cerebral artery occlusion (tMCAO) for 1 h. Estrogen and progesterone combination was immediately injected after tMCAO subcutaneously. Sensorimotor functional tests for evaluating behavioral deficits and TTC staining for measurement of infarct volume were performed 24 h after MCAO. Real-time PCR technique was used for gene expression analysis of glutamate transporters EAAT2 and EAAT3. Results: The combination of estrogen and progesterone could significantly reduce lesion volume. Also, hormone therapy could improve ischemic neurological disorders. After hormone therapy, gene expression of glutamate transporters EAAT2 and EAAT3 did not show significant changes. Conclusion: Combined estrogen–progesterone treatment significantly reduces neurological deficits and infarct volume; these effects are independent of the glutamate transporters signaling pathways.

Keywords

• Estrogen
• Glutamate transporters
• Ischemic stroke
• Progesterone
• Rats