Gender issues in the neurobiology of epilepsy: A clinical perspective

Koppel, Barbara S.; Harden, Cynthia L.

doi:10.1016/j.nbd.2014.08.033

Cited by 23 publications

(14 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7,8,10 Sex hormones contribute to the emergence of several forms of epilepsy at puberty and recede after menopause. 31 We observed a similar sex-dependent crossover for the cumulative probability of seizures in LQTS1 and LQTS2 participants during adolescence, and female sex (age 15-40 years) was a biomarker for seizures.…”

Section: Study Approval the Lqts Registry Was Approved By Thesupporting

confidence: 56%

Genetic biomarkers for the risk of seizures in long QT syndrome

et al. 2016

View full text Add to dashboard Cite

show abstract

Section: Study Approval the Lqts Registry Was Approved By Thesupporting

confidence: 56%

Genetic biomarkers for the risk of seizures in long QT syndrome

et al. 2016

View full text Add to dashboard Cite

show abstract

“…This is another major issue for lack of clinical relevance to aged population, especially to women, because of potential sex differences in stroke outcomes. Age and sex differences are much more prevalent in stroke and also are widely recognized in rodent models (Bake et al, ; Giorgi et al, ; Koppel and Harden, ; Sohrabji et al, ). Stroke studies have shown that young females have a smaller infarct and better cerebral blood flow than age‐matched males (Alkayed et al, ).…”

Section: Poststroke Epileptogenesismentioning

confidence: 99%

Prospects of modeling poststroke epileptogenesis

Reddy

Bhimani

Kuruba

et al. 2016

J of Neuroscience Research

View full text Add to dashboard Cite

This article describes the current status of post-stroke epilepsy (PSE) with an emphasis on post-stroke epileptogenesis modeling for testing new therapeutic agents. Stroke is a leading cause of epilepsy in an aging population. Late-onset “epileptic” seizures were reported in up to 30% cases after stroke. Nevertheless, the overall prevalence of PSE is 2–4%. Rodent models of stroke have contributed to our understanding of the relationship between seizures and the underlying ischemic damage to neurons. To understand whether acutely generated stroke events lead to a chronic phenotype more closely resembling PSE with recurrent seizures, a limited variety of approaches emerged in early 2000s. These limited methods of causing an occlusion in mice and rats show different infarct size and neurological deficits. The most employed procedure for inducing focal ischemia is the middle cerebral artery occlusion. This mimics the pathophysiology seen in humans, in terms of extent of damage to cortex and striatum. Photothrombosis and endothelin-1 models can similarly evoke episodes of ischemic stroke. These models are well suited to studying mechanisms and biomarkers of epileptogenesis or optimizing novel drug discoveries. However, modeling of PSE is tedious, highly variable, and lacks validity; therefore, is not widely implemented in epilepsy research. Moreover, the relevance of ischemic models to specific forms of human stroke remains unclear. Stroke modeling in young male rodents lacks clinical relevance to elderly population and especially women, due likely to sex differences. Nevertheless, owing to the neuronal damage and epileptogenic insult that these models trigger, they are helpful tools used to study acquired epilepsy and prophylactic drug therapy.

show abstract

“…

…”

mentioning

confidence: 99%

The Perimenstrual Delta Force: A Trojan Horse for Neurosteroid Effects

Galanopoulou¹

2015

Epilepsy Curr

View full text Add to dashboard Cite

CommentaryHormones influence neuronal excitability and seizure susceptibility in both adulthood and during development (1)(2)(3)(4)(5)(6)(7)(8). A paradigm illustrating these interactions is catamenial epilepsy, where seizures may cluster around specific periods of the menstrual cycle (3). The perimenstrual (C1) type of catamenial epilepsy is a type of epilepsy in which seizures cluster around the menstrual phase when estradiol, progesterone, as well as the neurosteroid allopregnanolone decline. Allopregnanolone is a progesterone metabolite known to act on GABA A receptors. Progesterone is converted to 5a-dihydroprogesterone (5a-DHP) by 5a-reductase, and then 5a-DHP is converted to allopregnanolone by 3b-hydroxysteroid dehydrogenase (3b-HSD).Reddy's team has been a pioneer in studies aiming to shed light in the molecular and pathophysiological mechanisms of increased seizure susceptibility in perimenstrual epilepsy. To recreate the hormonal and neurosteroid changes occurring during this perimenstrual period, they introduced a model of neurosteroid withdrawal (NSW) in adult female mice by administering high dose progesterone twice daily for 7 days followed by finasteride, a 5a-reductase inhibitor that blocks neurosteroid synthesis (8). This NSW model recreates high levels of allopregnanolone during the progesterone administration phase, which rapidly decline to normal levels during NSW. Interestingly, NSW mice demonstrate increased susceptibility to kindling associated with increased expression of the a4 GABA A receptor subunit in the dentate gyrus granule cells (8). The Carver et al. study completes these findings by showing a parallel increased expression of the d GABA A receptor subunit, a common partner of a4 in extrasynaptic GABA A receptors, as well as enhanced allopregnanolone potentiation of tonic but also phasic GABA A receptor currents in NSW mice. Such findings would be normally considered as capable of evoking antiseizure effects by increasing tonic inhibition. However, the authors found smaller tonic GABA current shifts in NSW granule cells compared to controls in the absence of added GABA, possibly suggesting the existence of silent GABA A receptors or low extracellular GABA in NSW hippocampus. In d knock-out Neurosteroids are endogenous regulators of neuronal excitability and seizure susceptibility. Neurosteroids, such as allopregnanolone (AP; 3α-hydroxy-5α-pregnan-20-one), exhibit enhanced anticonvulsant activity in perimenstrual catamenial epilepsy, a neuroendocrine condition in which seizures are clustered around the menstrual period associated with neurosteroid withdrawal (NSW). However, the molecular mechanisms underlying such enhanced neurosteroid sensitivity remain unclear. Neurosteroids are allosteric modulators of both synaptic (αβγ2-containing) and extrasynaptic (αβδ-containing) GABA A receptors, but they display greater sensitivity toward δ-subunit receptors in dentate gyrus granule cells (DGGCs). Here we report a novel plasticity of extrasynaptic δ-containing GABA A receptors in the den...

show abstract

Gender issues in the neurobiology of epilepsy: A clinical perspective

Cited by 23 publications

References 53 publications

Genetic biomarkers for the risk of seizures in long QT syndrome

Genetic biomarkers for the risk of seizures in long QT syndrome

Prospects of modeling poststroke epileptogenesis

The Perimenstrual Delta Force: A Trojan Horse for Neurosteroid Effects

Contact Info

Product

Resources

About