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Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins
Published on: August 15, 2017
Neurosteroid replacement therapy for catamenial epilepsy
Doodipala S Reddy1, Michael A Rogawski
1Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M System Health Science Center, College Station, Texas 77843, USA. reddy@medicine.tamhsc.edu
Catamenial epilepsy involves cyclical seizures linked to menstruation, potentially caused by falling progesterone and neurosteroid withdrawal. Neurosteroid replacement therapy, using drugs like ganaxolone, may prevent these perimenstrual seizure exacerbations.
Area of Science:
- Neuroscience
- Pharmacology
- Epilepsy Research
Background:
- Perimenstrual catamenial epilepsy affects many women with drug-refractory epilepsy, characterized by cyclical seizure exacerbations.
- This heightened seizure susceptibility is linked to the decline in progesterone and its metabolite, allopregnanolone, a GABA(A) receptor modulator, during menstruation.
Purpose of the Study:
- To investigate the neurobiological mechanisms underlying perimenstrual catamenial epilepsy.
- To evaluate the efficacy of neurosteroids as a treatment for catamenial seizures.
Main Methods:
- Utilized a rat pseudopregnancy model to simulate neurosteroid withdrawal and assess seizure susceptibility.
- Examined the effects of neurosteroid withdrawal on anticonvulsant drug potency and GABA(A) receptor expression in an epilepsy model.
Main Results:
- Neurosteroid withdrawal in rats increased susceptibility to chemoconvulsant seizures and spontaneous seizures.
- Anticonvulsant drug efficacy (benzodiazepines, valproate) was reduced, while neurosteroids (allopregnanolone, ganaxolone) showed enhanced potency.
- Changes in GABA(A) receptor subunit expression (e.g., alpha4) correlated with benzodiazepine resistance and altered neurosteroid sensitivity.
Conclusions:
- Neurosteroid withdrawal significantly impacts seizure threshold and anticonvulsant drug effectiveness.
- Neurosteroids and their analogs, like ganaxolone, show promise for treating catamenial epilepsy via neurosteroid replacement therapy.
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