Abstract:
:Evidence shows neurosteroids play a key role in regulating epileptogenesis. Neurosteroids such as testosterone modulate seizure susceptibility through its transformation to metabolites which show proconvulsant and anticonvulsant effects, respectively. Reduction of testosterone by aromatase generates proconvulsant 17-β estradiol. Alternatively, testosterone is metabolized into 5α-dihydrotestosterone (5α-DHT) by 5α-reductase, which is then reduced by 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR) to form anticonvulsant metabolite 3α-androstanediol (3α-Diol), a potent GABAA receptor modulating neurosteroid. The present study evaluated whether inhibition of aromatase inhibitor letrozole protects against seizures and neuronal degeneration induced by kainic acid (KA) (10 mg/kg, i.p.) in Swiss albino mice. Letrozole (1 mg/kg, i.p.) administered one hour prior to KA significantly increased the onset time of seizures and reduced the% incidence of seizures. Pretreatment with finasteride, a selective inhibitor of 5α-reductase and indomethacin, a selective inhibitor of 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR), reversed the protective effects of letrozole in KA-induced seizures in mice. Microscopic examination using cresyl violet staining revealed that letrozole did not modify KA-induced neurotoxicity in the CA1, CA3 and DG region of the hippocampus. Letrozole treatment resulted in the reduced levels of 17-β estradiol and elevated the levels of 5α-dihydrotestosterone (DHT) and 3α-Diol in the hippocampus. Finasteride and indomethacin attenuated letrozole-induced elevations of 5α-DHT and 3α-Diol. Our results indicate the potential anticonvulsant effects of letrozole against KA-induced seizures in mice that might be mediated by inhibiting aromatization of testosterone to 17β-estradiol, a proconvulsant hormone and by redirecting the synthesis to anticonvulsant metabolites, 5α-DHT and 3α-Diol. Acute aromatase inhibition, thus, might be used as an adjuvant in the treatment of status epilepticus and can be pursued further.
journal_name
Epilepsy Resjournal_title
Epilepsy researchauthors
Iqbal R,Jain GK,Siraj F,Vohora Ddoi
10.1016/j.eplepsyres.2018.04.004subject
Has Abstractpub_date
2018-07-01 00:00:00pages
60-69eissn
0920-1211issn
1872-6844pii
S0920-1211(18)30035-4journal_volume
143pub_type
杂志文章abstract:OBJECTIVE:We aim to delineate the genetic and clinical features of SCN8A developmental and epileptic encephalopathy. METHODS:Nine patients with SCN8A developmental and epileptic encephalopathy were included in this study. Genetic and clinical features and effectiveness of sodium channel blockers were assessed in patie...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2019.106222
更新日期:2019-12-01 00:00:00
abstract:INTRODUCTION:Rolandic epilepsy (RE) is an idiopathic focal childhood epilepsy with a well-established neuropsychological profile of language impairment. The aim of this study is to provide a functional correlate that links rolandic (sensorimotor) pathology to language problems using functional MRI. MATERIALS AND METHO...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.10.008
更新日期:2013-12-01 00:00:00
abstract::Comorbid conditions may affect the quality of life in persons with epilepsy (PWE) more than seizures. Using legally mandated healthcare encounter data, somatic, psychiatric, and neurodevelopmental comorbidities in a large population-based cohort of PWE, were compared to persons with migraine (PWM), a similar neurologi...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.12.002
更新日期:2014-02-01 00:00:00
abstract::The distribution and kinetics of specific binding sites for gamma-hydroxybutyrate (GHB), a naturally occurring compound known to produce absence-like seizures, was studied in the brains of Wistar rats with spontaneous, bilaterally synchronous spike wave discharges (SWDs), a model of petit mal epilepsy, and non-epilept...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(90)90097-f
更新日期:1990-11-01 00:00:00
abstract::It has previously been suggested that abnormalities in cardiac repolarization (QTc lengthening and shortening) are more likely to accompany seizures with hypoxemia and may be involved in sudden unexpected death in epilepsy (SUDEP). Accordingly, we evaluated for associations between peri-ictal QTc changes and hypoxemia...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2014.03.016
更新日期:2014-07-01 00:00:00
abstract::The novel anticonvulsant, remacemide HCl [(+/-)-2-amino-N-(1-methyl-1,2-diphenylethyl)acetamide monohydrochloride; FPL12924AA], and a desglycinated metabolite [(+/-)-1-methyl-1,2-diphenylethylamine monohydrochloride; FPL 12495AA] reversibly limited sustained high-frequency repetitive firing (SRF) of sodium-dependent a...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(95)00053-4
更新日期:1996-02-01 00:00:00
abstract::Outbred rats are widely used in biomedical research studies. The genotypic variation, different housing and handling conditions during development, and gender of used rats can be expected to cause variations in behavior and epileptogenesis. We tested the hypothesis that adult female Wistar rats from different breeders...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2010.12.012
更新日期:2011-03-01 00:00:00
abstract::Food intake triggers convulsions in fasted mice and rats treated with antimuscarinic drugs, scopolamine or atropine. Most of the drugs produced anticonvulsant efficacy in these convulsions have sedative effects. Thus, the present study was performed to evaluate the contribution of sedation in the suppression of convul...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2009.10.011
更新日期:2010-03-01 00:00:00
abstract::Post-stroke paroxysmal activity is a neurophysiological indicator of epileptogenesis and increase of seizure susceptibility, so treatments with neuroprotective activity and anti-paroxysmal activity can be more beneficial during post-ischemic period. The goal of this study was evaluation of levetiracetam (100 mg/kg, 7 ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2020.106466
更新日期:2020-11-01 00:00:00
abstract::Post-stroke seizures occur in 5-20% of patients. Modeling of stroke-induced seizures in animals provides a useful tool for investigating the molecular basis of epileptogenesis and for developing therapies for stroke patients at increased risk for epileptogenesis. The questions addressed in the study were: (1) Do rats ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(03)00034-2
更新日期:2003-04-01 00:00:00
abstract::Absence seizures are thought to be linked to abnormal interplays between regions of a thalamocortical network. However, the complexity of this widespread network makes characterizing the functional interactions among various brain regions challenging. Using whole-brain functional connectivity and network analysis of m...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2018.06.001
更新日期:2018-09-01 00:00:00
abstract::Huperzine A (HupA) is a naturally occurring compound found in the firmoss Huperzia serrata. While HupA is a potent acetylcholinesterase inhibitor, its full pharmacologic profile is incompletely described. Since previous works suggested a capacity for HupA to prophylax against seizures, we tested the HupA antiepileptic...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2015.08.012
更新日期:2015-11-01 00:00:00
abstract::Interpreting electrocorticography (ECoG) in the context of neuroimaging requires that multimodal information be integrated accurately. However, the implantation of ECoG electrodes can shift the brain impacting the spatial interpretation of electrode locations in the context of pre-implant imaging. We characterized the...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2020.106410
更新日期:2020-11-01 00:00:00
abstract:PURPOSE:Intracranial EEG in patients with lesional lateral temporal lobe epilepsy is rarely reported. Therefore, the number of patients with seizures arising independently from ipsilateral mesial structures or contralateral hemisphere has not been clarified. We analyzed the intracranial EEG of cases with localized lesi...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2007.10.009
更新日期:2008-01-01 00:00:00
abstract::Apolipoprotein E (ApoE) has been implicated as one of the susceptibility genes for temporal lobe epilepsy (TLE). Previous studies indicate that ApoE ɛ4 is associated with several disease-related traits including the increased risk of late posttraumatic seizures, earlier onset of TLE, refractory complex partial seizure...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2010.07.020
更新日期:2010-10-01 00:00:00
abstract::Fifty-eight patients with drug-resistant partial epilepsy were studied preoperatively by interictal rCBF measurements using 99mTc-HMPAO and a dedicated brain SPECT camera (Tomomatic 64). Follow-up of seizure outcome, using the "Engel score", was at least 3 years. The data were analyzed in a blinded set-up, first visua...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(96)00018-6
更新日期:1996-09-01 00:00:00
abstract:BACKGROUND:In many parts of eastern Asia, rice is a dietary staple and therefore the ketogenic diet (KD) can be difficult to administer. The aim of this study was to assess the long-term effectiveness and tolerability of the classical KD using a 2:1 ratio of fat to protein plus net carbohydrates, which is lower than th...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2018.09.002
更新日期:2018-11-01 00:00:00
abstract::Traumatic brain injury (TBI) is a leading cause of symptomatic epilepsy in young adults. This study examined physiological and anatomical epileptogenic consequences of a prior incident of TBI in rats. Rats were subjected to a fluid percussion brain injury one week prior to experimentation, and in vitro electrophysiolo...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(96)00044-7
更新日期:1996-12-01 00:00:00
abstract::Catamenial epilepsy is a multifaceted neuroendocrine condition in which seizures are clustered around specific points in the menstrual cycle, most often around perimenstrual or periovulatory period. Generally, a twofold or greater increase in seizure frequency during a particular phase of the menstrual cycle could be ...
journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/j.eplepsyres.2009.02.017
更新日期:2009-07-01 00:00:00
abstract:OBJECTIVE:to determine the feasibility as well as the attitudes among caregivers of children and adolescents with epilepsy in China towards the use of smart phone applications (apps) for the management of seizures. METHODS:The caregivers of children and adolescents with epilepsy, ages ranging from 0 to 15 years, were ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2016.08.002
更新日期:2016-11-01 00:00:00
abstract::Recognition of the role of genetics in the epilepsies has increased dramatically, impacting on clinical practice across many epilepsy syndromes. There is limited research investigating the impact of gene identification on individuals and families with epilepsy. While research has focused on the impact of delivering ge...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2015.02.011
更新日期:2015-05-01 00:00:00
abstract::Focal epilepsy (FE) is one of the most common forms of adult epilepsy and is usually regarded as a multifactorial disorder. Febrile seizures (FS) often appear during childhood in a subtype of FE patients, i.e. with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). FS are the most common human convulsive eve...
journal_title:Epilepsy research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.eplepsyres.2013.10.007
更新日期:2014-01-01 00:00:00
abstract:OBJECTIVE:This was the first proof of principle clinical trial assessing the efficacy and safety of rufinamide as adjunctive therapy in epileptic patients. The pharmacokinetic (PK) profile of rufinamide was also determined. METHODS:Fifty patients with diagnoses of partial or primary generalized tonic-clonic seizures w...
journal_title:Epilepsy research
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0920-1211(00)00185-6
更新日期:2001-02-01 00:00:00
abstract::Sodium valproate is a drug widely used for the treatment of epilepsy and mood disorders. We studied the effect of valproate on cerebral energy metabolism by incubating rat brain slices with 5 mM [3-(13)C]glutamate in the absence and the presence of 1 mM valproate. Substrate removal and product formation were measured ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2011.10.028
更新日期:2012-03-01 00:00:00
abstract::In the immature brain the neurotransmitter γ-amino butyric acid (GABA) mediates a membrane depolarization and can contribute to both, inhibition and excitation. Therefore the consequences of a positive modulation of GABA(A) receptors by neurosteroids on epileptiform activity are hard to predict. In order to analyze wh...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2019.106196
更新日期:2019-11-01 00:00:00
abstract::An earlier pharmacodynamic study of the chiral antiepileptic drug stiripentol in an intravenous pentylenetetrazol-induced seizure model in the rat showed the development of a significant degree of tolerance to the anticonvulsant and neurotoxic effects following subacute treatment with the racemic compound. A more rece...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(94)90001-9
更新日期:1994-06-01 00:00:00
abstract::A strain of Wistar rats, genetic absence epilepsy rats from Strasbourg (GAERS), was selected and inbred over 40 generations for occurrence of spontaneous spike-wave discharges characteristic of absence seizures, simultaneously with a strain of non-epileptic rats (NER). GAERS demonstrate an excessive sensitivity to ant...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(01)00292-3
更新日期:2001-11-01 00:00:00
abstract:PURPOSE:In patients with left temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) decreased naming ability is common, suggesting a critical role for the medial left temporal lobe in this task. We investigated the integrity of language networks with functional MRI (fMRI) in controls and TLE patients. EXPERIM...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2011.04.007
更新日期:2011-08-01 00:00:00
abstract::This paper reports the first systematic review of uncommon causes of status epilepticus reported in the literature between 1990 and 2008. Uncommon causes are defined as those not listed in the main epidemiological studies of status epilepticus. 181 causes were identified. These were easily categorised into 5 specific ...
journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/j.eplepsyres.2010.07.015
更新日期:2010-10-01 00:00:00
abstract:BACKGROUND:Idiopathic epilepsy (IE) is a syndrome that comprises epilepsy only, with no underlying structural brain lesion or other neurological signs or symptoms. Numerous studies have shown that genetic factors play an important role in IE. IE is a common disease in the Chinese Han population. However, the genetic ep...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2011.09.013
更新日期:2012-02-01 00:00:00