Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the present study was to examine seizure activity during reduced 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) production. Ovariectomized Long-Evans rats were stereotaxically implanted with bipolar electrodes above the perforant pathway; silastic implants filled with estradiol-17-benzoate (EB) and progesterone were inserted subcutaneously to mimic diestrus. Estrus was then induced in half of these animals by injection of EB (30 microg) and progesterone (2.5 mg), 48 and 4 h, respectively, prior to perforant pathway stimulation. Half of the estrous and diestrous rats also received a 5alpha-reductase inhibitor, finasteride (50 mg/kg), 6 h prior to perforant pathway stimulation. The estrous condition was associated with reduced number and duration of partial seizures, improved performance on a Morris water maze recovery of function test, reduced neuronal loss in the hilar region of the hippocampus, and elevated central and plasma 3alpha,5alpha-THP, compared to estrus+finasteride, diestrus+vehicle and diestrus+finasteride conditions, which did not differ from each another. These data suggest antiseizure effects of estrus may be caused, in part, by the action of 3alpha,5alpha-THP and that the precipitous decline in 3alpha,5alpha-THP may restore seizure threshold to control levels.
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PMID:Finasteride blocks the reduction in ictal activity produced by exogenous estrous cyclicity. 963 Mar 99

These studies investigate whether the neurosteroid and 5 alpha-reduced metabolite of testosterone (T), 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-Diol), has anti-seizure effects similar to its parent compound. In experiment 1, ovariectomized (ovx) Long-Evans rats (n = 20) were subcutaneously (s.c.) administered 32 mg/kg kainic acid or saline vehicle 10 min following 0.0, 3.0, or 7.5 mg/kg 3 alpha-Diol in 10% ethanol, propylene glycol vehicle (veh). During 2 h of observation of ictal activity, 3 alpha-Diol (3.0 and 7.5 mg/kg) prior to kainic acid significantly decreased the number and duration of partial and full seizures compared to the 0.0 3 alpha-Diol conditions and produced ictal activity that was comparable to 0.0 mg/kg 3 alpha-Diol no kainic acid controls (procedure controls). Animals that received 7.5 mg/kg 3 alpha-Diol prior to kainic acid had shorter latencies and distances to the hidden platform in a Morris Water Maze task than those that received 0.0 3 alpha-Diol, 1 week following ictal activity. Administration of 3 alpha-Diol (3.0 or 7.5 mg/kg) prior to kainic acid stimulation resulted in a greater number of identifiable neurons in the hilar region of the hippocampus, compared to 0.0 3 alpha-Diol condition. Experiment 2 was conducted to ascertain whether 3 alpha-Diol's anti-seizure effects were comparable to T and possibly a result of metabolism from T. Ovx rats (n = 36) were stereotaxically implanted with bipolar electrodes into the perforant pathway. One hour prior to perforant pathway stimulation, six rats were s.c. injected with either T (7.5 mg/kg), 3 alpha-Diol (7.5 mg/kg), 7.5 mg/kg T + 4MA (a 5 alpha-reductase inhibitor, 17 beta-N,N-diethylcarbamoyl-4-methyl-4aza,5 alpha-androstan-3-one), 4MA alone, 10% propylene glycol vehicle (veh) with perforant pathway stimulation, or veh without perforant pathway stimulation. 3 alpha-Diol and T produced similar seizure activity, water maze performance, and neuronal integrity in the hilar region of the hippocampus that were comparable to unstimulated controls. Because the T and 3 alpha-Diol groups were not different from T + 4MA but tended to be different from 4MA alone on these measures, this suggests that 3 alpha-Diol and T can have similar anti-seizure effects which may be due to actions of neurosteroids.
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PMID:Androgenic neurosteroids: anti-seizure effects in an animal model of epilepsy. 969 38

The asymmetrical breakdown of the blood-brain barrier to Evans-blue was studied in male and female rats during epileptiform seizures and in acute hypertension. The animals were divided into six groups. Group I: control female; Group II: control male; Group III: female + acute hypertension; Group IV: male + acute hypertension; Group V: female + seizure; Group VI: male + seizure. Asymmetric breakdown of the blood-brain barrier had been seen in female rats treated with pentylenetetrazol. Pentylenetetrazol-induced seizure produces less disruption of the blood-brain barrier in right cerebral hemisphere than in left cerebral hemisphere in female rats. There were no asymmetrical changes of blood-brain barrier permeability between the left and right hemispheres in acute hypertension in both sexes, and male rats treated with pentylenetetrazol.
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PMID:Asymmetrical changes in blood-brain barrier permeability during pentylenetetrazol-induced seizures and in acute hypertension. 975 55

The changes in the permeability of the blood-brain barrier (BBB) during bicuculline-induced seizures were investigated in ovariectomized female and orchidectomized male rats. The rats were anesthetized with diethyl ether. Evans blue, which was used as a BBB tracer, was injected into femoral vein 5 min before administering bicuculline to induce grandmal seizures. Ten groups of rats were studied: Group I: control female; Group II: control male; Group IIl: intact female + bicuculline; Group IV: intact male + bicuculline; Group V: ovariectomized female; Group VI: orchidectomized male; Group VII: ovariectomized female + bicuculline; Group VIII: orchidectomized male + bicuculline (1.2 mg/kg, i.v.); Group IX: ovariectomized female + estrogen + bicuculline; Group X: orchidectomized male + estrogen + bicuculline. Adult male and female rats were orchidectomized and ovariectomized 3 weeks before the experiments, or sham operated under general anesthesia. During bicucculline-induced seizures, the mean arterial blood pressure increased significantly in both intact and ovariectomized and orchidectomized rats. BBB lesions were present in 80 percent of intact female rats and 50 percent of ovariectomized rats after bicuculline-induced seizures. This difference between intact and ovariectomized rats was found to be significant (p < 0.01). There was no statistically significant change in the BBB permeability between intact and orchidectomized rats after convulsion. Generating seizures in both ovariectomized and orchidectomised rats, after administrating of estrogen, did not lead to any significant alteration in BBB permeability. Our results suggest that the extravasation of Evans blue albumin was most pronounced in the brain of intact female rats when compared to ovariectomized rats after bicuculline-induced seizures. After administrating estrogen, the decreased BBB permeability values of ovariectomised rats could not reach the values in intact rats.
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PMID:Influence of orchidectomy and ovariectomy on the blood-brain barrier permeability during bicuculline-induced seizures. 976 79

To examine the role of progesterone (P) and its 5alpha-reduced metabolite, the neurosteroid 5alpha-pregnan-3alpha-ol-20-one (3alpha, 5alpha-THP), in endogenous variations in ictal activity rats were tested for kainic acid-induced seizures in different hormonal milieu. Corresponding plasma and central P and 3alpha,5alpha-THP levels were measured. Cycling Long-Evans rats in estrus and proestrus had seizures of significantly shorter duration and more central and plasma 3alpha,5alpha-THP and P than animals in metestrus or diestrus. Females with luteal functioning had seizures of significantly shorter duration and increased central and plasma 3alpha,5alpha-THP and P compared to animals that recently had luteal functioning discontinued. Pregnant rats had significantly shorter seizures and greater central and plasma 3alpha,5alpha-THP and central P than animals tested 1-2 days postparturition. In all test paradigms, seizure activity was increased in animals that had decreased 3alpha, 5alpha-THP or P; overall, central 3alpha,5alpha-THP was more inversely related to ictal activity than central P or plasma P and 3alpha,5alpha-THP. To investigate a causal relationship between 3alpha,5alpha-THP and seizures, a 5alpha-reductase inhibitor, finasteride, or vehicle was administered to pregnant rats. Finasteride administration significantly decreased central and plasma 3alpha,5alpha-THP, but had no significant effect on plasma or central P of pregnant rats. Finasteride, but not vehicle administration, to pregnant rats significantly increased seizure duration. These findings support the hypothesis that variations in seizure threshold over endogenous hormonal milieu may be related to endogenous 3alpha,5alpha-THP. Of all of the endocrine conditions, seizure durations were greatest in diestrus animals; this group did not experience the lowest or the greatest decrease in 3alpha, 5alpha-THP concentrations; however, of all of the endocrine conditions, cycling rats experienced the most rapid cycles of 3alpha, 5alpha-THP variation. This suggests that cycles of endogenous variations in 3alpha,5alpha-THP may influence seizure threshold.
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PMID:Seizure activity is increased in endocrine states characterized by decline in endogenous levels of the neurosteroid 3 alpha,5 alpha-THP. 977 42

The abundance of mRNAs encoding various subunits of the gamma-aminobutyric acid type A (GABAA) receptor was examined in different regions of the brain of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease (WD). The measurements were performed at two different stages of disease: at 9 weeks of age, when no symptoms are evident, and at 15 weeks of age, when 90% of the animals develop jaundice. The amounts of the gamma2L and gamma2S subunit mRNAs in the striatum, cerebellum, and cerebral cortex of LEC rats at 9 weeks of age were increased (+25 to +35%) compared with those in LE rats of the same age; these differences were no longer apparent in 15-week old animals. The amount of alpha1 subunit mRNA was also significantly increased (+30%) in the cerebellum of LEC rats at 9 weeks of age; although a smaller increase (+20%) was still evident at 15 weeks of age, this was not statistically significant. The amount of beta2 subunit mRNA was increased in the cerebellum (+32%) and hippocampus (+21%) of LEC rats at 9 weeks of age, but no differences with LE rats were apparent at 15 weeks. The onset of isoniazid-induced seizures in LEC rats at 9 weeks of age was significantly delayed compared with that in LE rats. These results demonstrate abnormal expression of GABAA receptor subunit genes in the brain of LEC rats, and they suggest that this altered expression is associated with an increase in GABAergic tone.
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PMID:Increased abundance of GABAA receptor subunit mRNAs in the brain of Long-Evans Cinnamon rats, an animal model of Wilson's disease. 987 78

Antiseizure effects of progesterone (P) and its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha, 5alpha-THP) were investigated following continuous vs. discontinuous P exposure. In Experiments 1, 32 cycling Long-Evans rats were administered kainic acid (32 mg/kg SC), ictal behavior was examined, and plasma 3alpha,5alpha-THP levels were measured by radioimmunoassay. Proestrus/estrus rats showed less ictal activity and had elevated 3alpha,5alpha-THP levels prior to kainic acid compared to diestrus/metestrus subjects. In Experiment 2, 49 ovariectomized (ovx) rats were SC injected with estradiol benzoate (EB; 10 microg) and P (500 microg), to mimic estrus, or sesame oil vehicle (0.2 cc); all subjects were administered kainic acid. Rats tested with EB+P showed a reduced mean duration of full seizures and increased 3alpha,5alpha-THP, whereas those tested 24 h following EB+P had more tonic clonic seizures and lower 3alpha,5alpha-THP concentrations, comparable to ovx control animals. In Experiment 3, 49 ovx rats were stereotaxically implanted with bipolar electrodes into the perforant pathway. Prior to perforant pathway stimulation, rats received cholesterol or EB+P capsules for 1 month, continuously or intermittently. Irrespective of continuous or intermittent EB+P, the presence of progestins at the time of perforant pathway stimulation reduced partial seizure activity. Continuous EB+P capsules resulted in increased 3alpha,5alpha-THP levels compared to all other conditions, and less damage in the hilus of the hippocampus, compared to intermittent EB+P. These data confirm that P and 3alpha,5alpha-THP have antiseizure effects, and further suggest that repeated cycles of endogenous or exogenous P and/or 3alpha,5alpha-THP withdrawal influences seizure threshold and/or hippocampal integrity.
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PMID:Cyclic withdrawal from endogenous and exogenous progesterone increases kainic acid and perforant pathway induced seizures. 997 99

Audiogenic seizure susceptibility in the normally seizure-resistant Long-Evans rat may result from altered processing in the auditory pathway. Representative waveform latencies of the auditory brainstem responses (ABR) were recorded to examine generator alterations at different levels of the auditory neuraxis. Male Long-Evans rats primed for audiogenic seizures (AGS) on PND 14 with a 10 kHz pure tone at 120 dB SPL for 8 min were tested for AGS on PND 28 with 120 dB SPL continuous white noise. Primed subjects displayed wild running culminating in clonic convulsions. Following behavioral testing at 4-6 months, vertex recordings of ABR waves Ia-VI were made in anesthetized subjects using pure tone stimulus bursts. AGS subjects showed marginally elevated ABR thresholds. Shorter ABR wave latencies were elicited in AGS subjects for peripheral and central auditory components with stimulus intensities above 50 dB PeSPL at 8 and 40 kHz. Interpeak intervals were reduced for waves Ia-V and III-V in AGS subjects. These results reveal that intense sound stimulation during a sensitive period of development later reduces processing time at higher intensity levels.
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PMID:Latency alterations of the auditory brainstem response in audiogenic seizure-prone Long-Evans rats. 1002 64

This study was designed to evaluate the blood-brain barrier permeability characteristics of the WAG/Rij strain of rats that are an ideal model for human absence epilepsy, in controls and pentylenetetrazole-induced seizures conditioned to Evans blue-albumin. For this, WAG/Rij and Wistar rats were treated with either saline or 55 mg kg-1 pentylenetetrazole i.v. after the rats were injected with 3 ml kg-1 of 2% Evans blue. Total duration of seizure activity and regional blood-brain barrier permeability changes were determined and compared with control Wistar rats. The duration of convulsive activity which was induced by pentylenetetrazole was significantly longer in WAG/Rij rats than in Wistar rats. The blood-brain barrier opening to Evans blue was not the case in saline- injected WAG/Rij or Wistar rats, but this was clearly seen in both strains after pentylenetetrazole-induced convulsions. EB leakage was mainly seen in the cortical areas, cerebellum, pons, thalamus, hypothalamus and corpus striatum of WAG/Rij rat brain, whereas this was recorded in the preoptic area, bulbus olfactorius, midbrain, hypothalamus, corpus striatum and inferior colliculus of the Wistar rats brain. As a result, the WAG/Rij rats were more susceptible than Wistar rats to PTZ-induced generalised tonic-clonic convulsions, and a different pattern in PTZ-induced changes in BBB permeability was observed between WAG/Rij rats and Wistar rats.
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PMID:Absence epilepsy and regional blood-brain barrier permeability: the effects of pentylenetetrazole-induced convulsions. 1020 61

The Long-Evans rat is a hybrid rodent strain with little innate susceptibility to audiogenic seizures (AGS). The present study examines parameters of acoustic priming (induced susceptibility) and testing for AGS during postnatal development subsequent to auditory function, and identifies the effects of stimulus intensity, repeated testing, and gender upon AGS activity. Rats were exposed to 125-dB SPL 10-kHz tone bursts at 14-36 days of age and tested with white noise at 14 or 19 days following sound exposure. All priming/testing combinations yielded AGS susceptibility; animals primed at 18 days showed the highest incidence of clonic seizures when tested 14 days later. All subjects displayed clonus at testing intensities of 120 dB, although some seizure behaviors could be elicited at 100 dB. Repeated testing at 120 dB increased latency to clonus and clonus duration, and total wild running activity. Gender differences for AGS expression were minimal. These results demonstrate the viability of the seizure-resistant Long-Evans rat for study of AGS.
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PMID:Audiogenic seizures in the developmentally primed Long-Evans rat. 1033 Nov 54


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