The anticonvulsant effects of progesterone and its metabolites on amygdala-kindled seizures in male rats

Lonsdale, Deborah; Nylen, Kirk; Burnham, W. McIntyre

doi:10.1016/j.brainres.2006.05.005

Cited by 24 publications

(13 citation statements)

References 20 publications

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“…In the same model, PROG and ALLO protected against secondarily generalized seizures, being ineffective or effective only at toxic doses against focal seizures. On the other hand, 5α-DHP inhibited both components of seizures (Lonsdale et al, 2006). Growing evidence suggests that anticonvulsive and neuroprotective properties of PROG are mediated by its metabolites 5α-DHP and ALLO, positive modulators of GABA A receptors (Reddy, 2004; Ciriza et al, 2006; Verrotti et al, 2010; Stevens and Harden, 2011).…”

Section: Progesterone and Derivativesmentioning

confidence: 99%

Neuroprotective Actions of Neurosteroids

Borowicz¹,

Piskorska²,

Banach³

et al. 2011

Front. Endocrin.

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Neurosteroids were initially defined as steroid hormones locally synthesized within the nervous tissue. Subsequently, they were described as steroid hormone derivatives that devoid hormonal action but still affect neuronal excitability through modulation of ionotropic receptors. Neurosteroids are further subdivided into natural (produced in the brain) and synthetic. Some authors distinguish between hormonal and regular neurosteroids in the group of natural ones. The latter group, including hormone metabolites like allopregnanolone or tetrahydrodeoxycorticosterone, is devoid of hormonal activity. Both hormones and their derivatives share, however, most of the physiological functions. It is usually very difficult to distinguish the effects of hormones and their metabolites. All these substances may influence seizure phenomena and exhibit neuroprotective effects. Neuroprotection offered by steroid hormones may be realized in both genomic and non-genomic mechanisms and involve regulation of the pro- and anti-apoptotic factors expression, intracellular signaling pathways, neurotransmission, oxidative, and inflammatory processes. Since regular neurosteroids show no affinity for steroid receptors, they may act only in a non-genomic mode. Multiple studies have been conducted so far to show efficacy of neurosteroids in the treatment of the central and peripheral nervous system injury, ischemia, neurodegenerative diseases, or seizures. In this review we focused primarily on neurosteroid mechanisms of action and their role in the process of neurodegeneration. Most of the data refers to results obtained in experimental studies. However, it should be realized that knowledge about neuroactive steroids remains still incomplete and requires confirmation in clinical conditions.

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Section: Progesterone and Derivativesmentioning

confidence: 99%

Neuroprotective Actions of Neurosteroids

Borowicz¹,

Piskorska²,

Banach³

et al. 2011

Front. Endocrin.

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“…These anti-seizure effects of progesterone are accredited to its metabolite allopregnanolone (3α-OH-5α-pregnan-20-one) (Frye et al, 2000; Frye et al, 2002; Herzog and Frye, 2003; Lonsdale et al, 2006). Effects of allopregnanolone are acute, non-genomic, and robust as expected from a positive allosteric modulator of GABA A receptors (Lambert et al, 2009).…”

Section: Mechanism-based Differences Between Effects Of Estradiol Andmentioning

confidence: 99%

Sex and hormonal influences on seizures and epilepsy

Velı́šková

DeSantis

2013

Hormones and Behavior

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Epilepsy is the third most common chronic neurological disorder. Clinical and experimental evidence supports the role of sex and influence of sex hormones on seizures and epilepsy as well as alterations of the endocrine system and levels of sex hormones by epileptiform activity. Conversely, seizures are sensitive to changes in sex hormone levels, which in turn may affect the seizure-induced neuronal damage. The effects of reproductive hormones on neuronal excitability and seizure-induced damage are complex to contradictory and depend on different mechanisms, which have to be accounted for in data interpretation. Both estradiol and progesterone/allopregnanolone may have beneficial effects for patients with epilepsy. Individualized hormonal therapy should be considered as adjunctive treatment in patients with epilepsy to improve seizure control as well as quality of life.

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“…Indeed, the incidence of epilepsy is generally lower in women than in men (Hauser et al, 1993; Christensen et al, 2005; McHugh and Delanty, 2008). This gender difference could be caused by ovarian hormones such as P. Although P is known to inhibit stimulation-evoked seizures in kindling models (Holmes and Weber, 1984; Mohammad et al, 1998; Lonsdale et al, 2006), P has not been investigated widely for its potential disease-modifying effect in epileptogenic models. In the amygdala kindling model, P has been shown to impair epileptogenesis in male rats (Holmes and Weber, 1984; Edwards et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Disease-modifying activity of progesterone in the hippocampus kindling model of epileptogenesis

2010

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Progesterone (P) is an endogenous anticonvulsant hormone. P is being evaluated as a treatment for epilepsy, traumatic brain injury, and other complex neurological conditions. Preclinical and clinical studies suggest that P appears to interrupt epileptogenic events. However, the potential disease-modifying effect of P in epileptogenic models is not widely investigated. In this study, we examined the effects of P on the development of hippocampus kindling in female mice. In addition, we determined the role of progesterone receptors (PR) in the P’s effect on the kindling epileptogenesis utilizing PR knockout (PRKO) mice. P, at 25 mg/kg, did not affect seizures and did not exert sedative/motor effects in fully-kindled mice. P treatment (25 mg/kg, twice daily for 2 weeks) significantly suppressed the rate of development of behavioral kindled seizure activity evoked by daily hippocampus stimulation in wild-type (WT) mice, indicating a disease-modifying effect of P on limbic epileptogenesis. There was a significant increase in the rate of ‘rebound or withdrawal’ kindling during drug-free stimulation sessions following abrupt discontinuation of P treatment. A washout period after termination of P treatment prevented such acceleration in kindling. PRKO mice were kindled significantly slower than WT mice, indicating a modulatory role of PRs in seizure susceptibility. P’s effects on early kindling progression was partially decreased in PRKO mice, but the overall (~2-fold) delay in the rate of kindling for the induction of stage 5 seizures was unchanged in PRKO mice. Moreover, the acute anticonvulsant effect of P was undiminished in fully-kindled PRKO mice. These studies suggest that P exerts disease-modifying effects in the hippocampus kindling model at doses that do not significantly affect seizure expression and motor performance, and the kindling-retarding effects of P may occur partly through a complex PR-dependent and PR-independent mechanism.

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The anticonvulsant effects of progesterone and its metabolites on amygdala-kindled seizures in male rats

Cited by 24 publications

References 20 publications

Neuroprotective Actions of Neurosteroids

Neuroprotective Actions of Neurosteroids

Sex and hormonal influences on seizures and epilepsy

Disease-modifying activity of progesterone in the hippocampus kindling model of epileptogenesis

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