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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sex steroid peripheral pattern, pulsatile luteinizing hormone (LH) secretion, gonadotropin and prolactin responses to LH-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) were studied in 35 male epileptics treated with phenobarbital (PB), carbamazepine (CBZ), or phenytoin (PHT), and in age-matched healthy males. Idiopathic generalized epilepsy (IGE) was diagnosed in 12 cases and partial epilepsy (PE) in 23 cases. Patients were seizure-free and did not show EEG abnormalities at repeated controls in the last 5 years, so that interfering effects of seizures were possibly excluded. The aim of the study was to evaluate both the role of epileptic syndromes and of anti-epileptic drugs on the endocrine function. Changes in sex hormone binding globulin, total and free testosterone, dihydrotestosterone and delta 4-androstenedione were found to be independent of the epileptic syndrome type. The LH response to LHRH was lower in PB-treated PE than in IGE subjects on the same drug regimen. An impairment of LH pulsatility with respect to controls was found in PE but not in IGE patients taking PB. Among antiepileptic drugs, PHT is associated with higher sex hormone binding globulin and estradiol and lower free testosterone and dihydrotestosterone levels. PB and CBZ, but not PHT, blunt the LH response to exogenous LHRH in PE. Prolactin responses to TRH were consistently enhanced in PE subjects treated with CBZ or PHT.
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PMID:Sex hormones, gonadotropins and prolactin in male epileptic subjects in remission: role of the epileptic syndrome and of antiepileptic drugs. 796 56

Determination of serum prolactin can help distinguish between epileptic and pseudo-epileptic attacks since generalized tonic-clonic and complex partial seizures frequently are accompanied by a transient rise in prolactin. In status epilepticus, however, serum prolactin levels are well within the normal range: cellular depletion due to the prolonged seizure activity has been suggested as a mechanism for this finding. The control of prolactin secretion is complex. Among several possible regulators, inhibitory dopamine and stimulatory thyrotropin-releasing hormone (TRH) may take part in the regulation of prolactin levels in connection with epileptic activity. There may be subpopulations of prolactin-producing cells that react differently in response to various regulators. A dopamine receptor blocker given during status epilepticus brings forth a distinct increase in prolactin levels. In order to add to the understanding of prolactin changes in connection with status epilepticus, we injected TRH i.v. during status epilepticus in seven consecutive patients. All patients had prolactin levels within the normal range (< 25 micrograms/l) before injection of TRH which resulted in at least a two-fold increase in prolactin levels. Our results contradict the hypothesis of cellular depletion of prolactin in connection with status epilepticus. The mechanism behind prolactin values within the normal range after prolonged seizure activity remains unknown.
Seizure 1993 Sep
PMID:Serum prolactin response to thyrotropin-releasing hormone during status epilepticus. 816 88

Hippocampal thyrotropin-releasing hormone (TRH) release was examined after seizures were induced by electroconvulsive shock (ECS). Rat hippocampal slices taken 12, 24, or 48 h after 3 days of alternate-day ECS treatment or sham-ECS treatment were stimulated with potassium with or without calcium in a superfusion system containing in-line charcoal adsorbent to concentrate TRH. Released TRH and tissue TRH were measured by radioimmunoassay. The TRH content of hippocampal slices was increased fivefold over sham-ECS levels 12, 24, and 48 h after ECS, but this was not associated with an increase in basal TRH release. Potassium-stimulated TRH release was significantly elevated over basal release 12, 24, and 48 h after ECS. Potassium-stimulated calcium-dependent TRH release increased linearly after ECS, reaching its highest level 48 h after seizure. Thus, although enhanced calcium-dependent TRH release was associated with elevated tissue levels, this relationship was not proportional in that tissue TRH was elevated to the same extent at all times after ECS, whereas potassium-evoked calcium-dependent TRH release increased gradually over time after seizure. These results suggest that postictal elevations in TRH are associated with an enhanced capacity for release that develops as a result of a time-dependent shift of TRH from a storage compartment ot a readily releasable pool. The observed elevation in stimulated TRH release may be relevant to seizure-induced modulation of TRH receptors in vivo.
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PMID:Thyrotropin-releasing hormone release is enhanced in hippocampal slices after electroconvulsive shock. 826 11

Previous studies using two seizure paradigms, electroconvulsive shock and kindling, suggested potential sites of endogenous thyrotropin-releasing hormone (TRH) action in specific epileptogenic areas. We studied TRH gene expression and TRH receptors in rat limbic areas using the kindling model of epilepsy. Immunoassayable TRH increased 4- to 20-fold over control levels in specific subregions of the hippocampus 24 hours after a single stage 5 seizure. Concurrently, TRH receptor binding was significantly reduced in hippocampal (23-39%) and amygdaloid (21-22%) membranes. Dramatic temporal and spatial changes in prepro-TRH messenger RNA were visualized by in situ hybridization histochemistry in the hippocampal dentate gyrus, the piriform cortex, and the amygdala. Peak hybridization occurred 6 and 12 hours postictally in these loci and returned toward basal levels by 24 hours. These results are consistent with the hypothesis that TRH may have an important role in the pathophysiology epilepsy by modulating excitatory processes.
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PMID:Thyrotropin-releasing hormone gene expression and receptors are differentially modified in limbic foci by seizures. 838 90

Spontaneously epileptic rats (SER), which represent a double mutation (zi/zi, tm/tm), spontaneously exhibit both tonic and absence-like seizures. We examine the long-term effects of a thyrotropin-releasing hormone (TRH) analogue, CNK-602A, acute administration of which was effective inhibiting both types of seizures in SER, to determine if this agent could be used to treat epilepsy for long periods. Food pellets containing 0.001% CNK-602A were given ad libitum to SER from age 7 weeks. CNK-602A significantly inhibited tonic convulsions and prolonged survival. There were no alterations in body weight or plasma levels of triiodotHyronine (T3) and thyroxine (T4). These findings indicate that chronic intake of CNK-602A in a dose that does not affect plasma levels of T3 and T4 inhibits tonic convulsions in SER and suggest that this drug may be an effective treatment for convulsive seizures in patients with epilepsy.
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PMID:Long-term antiepileptic effects of chronic intake of CNK-602A, a thyrotropin-releasing hormone analogue, on spontaneously epileptic rats. 860 36

It has previously been demonstrated that thyrotropin-releasing hormone (TRH) mRNA expression is dramatically increased in limbic structures including dentate gyrus granular layer, and pyriform, entorhinal and perirhinal cortices following amygdala kindling. Since thyroid hormone regulates TRH mRNA in the paraventricular nucleus of the hypothalamus (PVN), we investigated whether basal or kindling-induced TRH mRNA expression in limbic regions is also regulated by thyroid hormone. Hypo- and hyperthyroidism was induced by treating rats with 0.05% 6-n-propyl-2-thiouracil (PTU) (equivalent to approximately 30 mg/kg/day) or 0.9 microM 3,5,3'-triiodo-L-thyronine (T3) (equivalent to approximately 50 micrograms/kg/day), respectively, in their drinking water for 10 days before kindling and throughout the kindling procedure. Rats were sacrificed 4 h after their first stage 5 seizure. None of the thyroid hormone manipulations altered kindling development, or behavioral and electrographic after-discharge seizure durations. Pituitary TSH beta mRNA levels were significantly increased by PTU and suppressed by T3, but unaffected by kindling. In addition, in situ hybridization showed that PTU administration increased and T3 administration decreased TRH mRNA levels in the PVN, consistent with thyroid hormone's negative feedback effects. At the same time, kindling had no effect on TRH mRNA in the PVN. In contrast, kindling dramatically increased TRH mRNA in the dentate gyrus granular layer, and pyriform, entorhinal and perirhinal cortices, but thyroid hormone manipulations did not affect either basal or kindling-induced TRH mRNA expression in limbic structures. These findings demonstrate that TRH mRNA expression is differentially regulated in the hypothalamic PVN and limbic structures.
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PMID:Differential regulation of basal and kindling-induced TRH mRNA expression by thyroid hormone in the hypothalamic and limbic structures. 867 19

The effects of thyrotropin-releasing hormone (TRH) administration on electroconvulsive therapy (ECT)-induced prolactin (PRL) secretion and the duration of the seizure were studied in 14 depressed women. In a balanced order crossover design the patients were given 0.4 mg TRH or placebo intravenously 20 min before ECT during the first two sessions. In the third ECT session TRH was given just prior to ECT. ECT elicited the expected PRL response when given alone and when given 20 min after TRH when PRL plasma levels were high. During the coadministration design (third ECT session) PRL levels were raised not as a sum of the two stimuli but even significantly more. TRH failed to modify the duration of the seizure induced by ECT. Therefore, if TRH is involved in seizure modulation during ECT, our findings suggest a postictal rather than ictal role for TRH.
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PMID:Effects of thyrotropin-releasing hormone administration on the electroconvulsive therapy induced prolactin responses and seizure time. 867 90

Thyrotropin-releasing hormone and its receptor are differentially distributed throughout the limbic forebrain. In addition to its neuroendocrine function, several non-endocrine central nervous system effects of thyrotropin-releasing hormone and its analogs have been reported, including anticonvulsant effects in animals and humans. Kindling, as a model of temporal lobe epilepsy, produces elevations of endogenous thyrotropin-releasing hormone specifically in seizure-prone limbic regions. The present study used semi-quantitative in situ hybridization to characterize changes in thyrotropin-releasing hormone messenger RNA that occurred during the kindling process (partial kindling), as well as after fully kindled seizures. No significant change in thyrotropin-releasing hormone messenger RNA was detected 1 h postictally, whereas significant elevations were detected in the granule cell layer of the hippocampal dentate gyrus, diffuse nuclei of the amygdala and in layers II and III of piriform and entorhinal cortices from 3 to 48 h after a single generalized seizure in fully kindled rats. Peak messenger RNA expression occurred from 6 to 12 h postictally, with a decline at 24 h, followed by a precipitous return to undetectable levels by 48 h, except in the dentate gyrus. In marked contrast, partial kindling produced no detectable change in thyrotropin-releasing hormone messenger RNA by 6 h after the first occurrence of stage 1-5 seizures. Electrode placement, a single afterdischarge, or a 20-microA stimulation of the amygdala was not associated with accumulation of thyrotropin-releasing hormone messenger RNA. Thus, only full kindled generalized seizures increased thyrotropin-releasing hormone messenger RNA expression in identical limbic regions which also showed postictal elevations in thyrotropin-releasing hormone. However, this enhancement followed a more immediate and shorter lasting time-course than previously demonstrated increases in the tripeptide. These results support the hypothesis that thyrotropin-releasing hormone is an important neuromodulator in epileptic foci.
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PMID:Increases in thyrotropin-releasing hormone messenger RNA expression induced by a model of human temporal lobe epilepsy: effect of partial and complete kindling. 897 61

Endogenous thyrotropin-releasing hormone has been hypothesized to modulate seizure activity, possibly by subserving an anticonvulsant function in limbic brain. A specific and sensitive radioimmunoassay was utilized to quantitate thyrotropin-releasing hormone levels in dorsoventrally dissected hippocampal subregions after partially (an experimental paradigm of complex partial epilepsy) or fully kindled (repeated generalized) seizures, to define specific seizure-related limbic pathways that may contain thyrotropin-releasing hormone. Samples were taken from electrode controls and 1, 6, 24, 48 and 144 h after a fully kindled seizure or 24 h after the first occurrence of a stage 3-4 (partially kindled) seizure in rats. Thyrotropin-releasing hormone levels were below controls in all subregions taken 1 h after a fully kindled seizure. They resembled control values 6 h after seizure, were substantially elevated at 24 and 48 h, and then returned to control levels by 144h. Low thyrotropin-releasing hormone levels seen shortly after the seizure presumably indicate peptide depletion during the ictus. The higher levels seen at later times occurred during a postictal period coinciding with refraction to additional seizure-generating stimulation. These values probably reflect enhanced synthesis since the largest increases were seen in subregions (dentate gyrus, hilus/CA4, CA3) that contain perforant path terminals, and where previously observed intrinsic hippocampal thyrotropin-releasing hormone messenger RNA increases were seen. The thyrotropin-releasing hormone response was less robust in ventral hilus/CA4 and CA3 areas, leading to speculation that this smaller response could, in part, explain why the ventral (temporal) hippocampus may be more susceptible to seizure-induced damage. No changes in thyrotropin-releasing hormone were detected after partially kindled seizures, suggesting that thyrotropin-releasing hormone is not involved in epileptogenesis or its stereotypic motor behavior. The time-course and distribution of thyrotropin-releasing hormone elevations seen after a fully kindled (repeated generalized) seizure, and the lack of effect of partial kindling (complex partial seizure) are consistent with previous observations concerning postictal thyrotropin-releasing hormone messenger RNA expression. These neurochemical results support the hypothesis that endogenous thyrotropin-releasing hormone can serve an anticonvulsant neuromodulatory function in specific limbic pathways relevant to temporal lobe epilepsy.
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PMID:Changes in thyrotropin-releasing hormone levels in hippocampal subregions induced by a model of human temporal lobe epilepsy: effect of partial and complete kindling. 897 62

Soman is an organophosphorus (OP) compound which irreversibly inhibits acetylcholinesterase (AChE), the primary synaptic inactivator of acetylcholine. Resultant excessive cholinergic activity elicits generalized convulsions and brain lesions. Recent evidence suggests that other neurotransmitter/neuromodulator systems may be affected by the OP compounds as well. Since we have shown that both electrically and chemically induced seizures cause significant and prolonged increases in the neuropeptide thyrotropin-releasing hormone (TRH) in epileptogenic sites, we examined soman-induced convulsion effects on CNS TRH. Rats were injected with either soman (100 microg/kg SC; equivalent to 0.9 LD50) or saline and observed for convulsive activity. Forty-eight hours post injection, dramatic increases of TRH over control levels were seen in frontal cortex (30-fold), pooled cortex (24-fold), hippocampus (16-fold), piriform cortex (14-fold), entorhinal cortex (11-fold), and amygdala (2-fold). No change was observed in either hypothalamus or pituitary. Our results demonstrate, for the first time, a substantial effect of an OP on a specific neuropeptide system in vivo. The neurochemical and behavioral consequences of the soman-induced increases in TRH, especially in the frontal cortex, are presently unknown. Clearly, much more work is required to discern the exact role TRH has following soman exposure.
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PMID:Thyrotropin-releasing hormone (TRH) is markedly increased in the rat brain following soman-induced convulsions. 904 10


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