Neurosteroid Influences on Neuronal Excitability

Reddy, Doodipala Samba

doi:10.1002/9781118531037.ch3

Cited by 2 publications

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“…Nörosteroid seviyelerindeki dalgalanmalar nöbet kontrolünü güçleştirir. [66][67][68] Östrodiol/nörosteroid oranı menstruasyon sırasında en yüksek seviyededir. Nörosteroidler, GABA-A reseptör aracılı inhibisyonu güçlendirdiğinden, nörosteroid aracılı inhibisyonun, adet öncesi, sırası veya sonrasındaki hızlı kaybı, katameniyal epilepsili birçok kadında artmış nöbetlerin nedeni olabilir.…”

Section: Nörosteroidlerin Rolüunclassified

Katameniyal Epilepsi

Çelik¹

2018

Epilepsi

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When seizures occur in clusters during certain stages of the menstrual cycle (perimenstrual and periovulatory stages), it is defined as catamenial epilepsy. The prevalence varies between 10% and 70%. There are 3 patterns of catamenial epilepsy: perimenstrual (most common), periovulatory, and seizures in the insufficient luteal phase. In the pathophysiology of this occurrence, the neuroactive properties of the reproduction-associated steroid hormones (direct membrane-associated short-term effect and intracellular receptor/genomic-related longterm effect) and their cyclic changes in serum levels play a role in the susceptibility of the epileptogenic area to neuroactive steroids. Among steroid hormones, while progesterone and neurosteroids are known as anticonvulsants, estrogen, the best known proconvulsant, has been found in recent studies to also have anticonvulsant effects related to Neuropeptide Y. Hormonal (medroxyprogesterone acetate, clomiphene, triptorelin, leuprolide, progesterone, goserelin), non-hormonal (acetazolamide, clobazam, lamotrigine, levetiracetam), and neurosteroidbased therapies (ganaxolone) are used in the treatment of catamenial epilepsy. Seizure control and menstrual cycle maintenance, measurement of the blood level of antiepileptic drugs before and after menstruation and adjustment of the drug dosage as required, intermittent benzodiazepine administration, acetazolamide, or hormonal treatments such as oral contraceptives during menstruation are among the treatment strategies for catamenial epilepsy.

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Section: Nörosteroidlerin Rolüunclassified

Katameniyal Epilepsi

Çelik¹

2018

Epilepsi

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Catamenial Epilepsy: Discovery of an Extrasynaptic Molecular Mechanism for Targeted Therapy

Reddy

2016

Front. Cell. Neurosci.

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Catamenial epilepsy is a type of refractory epilepsy characterized by seizure clusters around perimenstrual or periovulatory period. The pathophysiology of catamenial epilepsy still remains unclear, yet there are few animal models to study this gender-specific disorder. The pathophysiology of perimenstrual catamenial epilepsy involves the withdrawal of the progesterone-derived GABAergic neurosteroids due to the decline in progesterone level at the time of menstruation. These manifestations can be faithfully reproduced in rodents by specific neuroendocrine manipulations. Since mice and rats, like humans, have ovarian cycles with circulating hormones, they appear to be suitable animal models for studies of perimenstrual seizures. Recently, we created specific experimental models to mimic perimenstrual seizures. Studies in rat and mouse models of catamenial epilepsy show enhanced susceptibility to seizures or increased seizure exacerbations following neurosteroid withdrawal. During such a seizure exacerbation period, there is a striking decrease in the anticonvulsant effect of commonly prescribed antiepileptics, such as benzodiazepines, but an increase in the anticonvulsant potency of exogenous neurosteroids. We discovered an extrasynaptic molecular mechanism of catamenial epilepsy. In essence, extrasynaptic δGABA-A receptors are upregulated during perimenstrual-like neuroendocrine milieu. Consequently, there is enhanced antiseizure efficacy of neurosteroids in catamenial models because δGABA-A receptors confer neurosteroid sensitivity and greater seizure protection. Molecular mechanisms such as these offer a strong rationale for the clinical development of a neurosteroid replacement therapy for catamenial epilepsy.

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Neurosteroid Influences on Neuronal Excitability

Cited by 2 publications

References 57 publications

Katameniyal Epilepsi

Katameniyal Epilepsi

Catamenial Epilepsy: Discovery of an Extrasynaptic Molecular Mechanism for Targeted Therapy

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