Background: Seizure is an abnormal electrical activity probably due to an imbalance between excitation and inhibition in the brain. Pentylenetetrazol (PTZ) is a chemical convulsive agent abundantly used in laboratory animals. PTZ induces a change in glutamate and GABA in the brain which this study investigates the persistence of this change.

Materials and Methods: In this experimental study, 18 male Wistar rats divided into 3 groups. Three i.v doses of PTZ 20, 25 and 30 mg/ml were used to determine the effective PTZ dose. Convulsive behaviors were monitored as tonic clonic and myoclonic twitches. Hippocampal glutamate and GABA contents were measured using a biochemical method.

Results: Dose of 20 was resulted in long latency to and short lasting TC convulsions with a high volume of injected PTZ solution. On the other hand, dose of 25 and 30 led to short latency and long lasting convulsions with low volume of injecting solution. However there was high rate of mortality (100%) in dose of 30 mg/ml. Hippocampal glutamate content was decreased in zero and 20 min groups while GABA content was decreased only in 20 min group.

Conclusion: It is concluded that dose of 25 is the appropriate i.v dose to induce TC convulsions in rats which decreases glutamate and GABA while increases the ratio of glutamate to GABA. Therefore, alteration of glutamate and GABA may be the basis for subsequent seizure induced changes.

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.