Abstract:
PURPOSE:We used the paired-pulse inhibition paradigm to determine whether the cell loss in the hilus of the dentate gyrus of female rats after kainic acid (KA)-induced status epilepticus (SE) is associated with functional changes in the dentate gyrus. Additionally, we determined whether the lost function could be preserved by using estrogen neuroprotection. METHODS:Female rats were ovariectomized and treated either with estrogen replacement (four doses of 2 microg of estradiol every 24 h: two doses before SE, two doses after) or oil. SE was induced by I.P. administration of KA (16 mg/kg) and terminated after 5 h with pentobarbital. After 2 days, hippocampal/dentate gyrus slices were prepared. Population spikes were recorded in the granule cell layer as a response to mixed perforant-path stimulation (10- to 1,000-ms interstimulus intervals). Ratios of the test response to conditioning response were evaluated. Gamma-aminobutyric acid type B (GABAB) receptors were blocked with 400 microM CGP 35348. RESULTS:In slices from oil-treated rats, SE induced a loss of paired-pulse inhibition in the dentate gyrus at the interstimulus intervals marking intermediate facilitation and late depression. There was no such loss of paired-pulse inhibition in estrogen-treated rats. CGP 35348 was unable to alter paired-pulse inhibition in slices form oil-treated rats. In slices from estrogen-treated rats, CGP decreased paired-pulse inhibition at 50-150-ms interstimulus intervals. Comparison of paired-pulse inhibition in slices from oil-treated rats with slices from estrogen-treated rats with CGP 35348 revealed a GABAB-independent difference at interstimulus intervals >300 ms. CONCLUSIONS:Our study demonstrated that there is a complete loss of GABAB receptor-mediated inhibition after KA-induced SE in the dentate gyrus. Pretreatment with estrogen can save GABAB-receptor function, probably by neuroprotection of neurons containing the postsynaptic GABAB receptors.
journal_name
Epilepsiajournal_title
Epilepsiaauthors
Velísek L,Velísková Jdoi
10.1046/j.1528-1157.43.s.5.3.xsubject
Has Abstractpub_date
2002-01-01 00:00:00pages
146-51eissn
0013-9580issn
1528-1167pii
epis6002journal_volume
43 Suppl 5pub_type
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