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

We examined the anticonvulsant effects of DN-1417 an analog of the thyrotropin-releasing hormone (TRH) in seizure-prone El mice. Changes in both immunoreactive TRH (IR-TRH) and TRH receptor binding activity in discrete brain regions of El mice were also measured before and after sensitization and during the postictal period, and they were compared with those in the ddY mice. Intraperitoneal injection of DN-1417 with 150 and 450 mg/kg significantly increased the El mouse seizure threshold in a dose-dependent manner. IR-TRH in the hippocampus of El mice, which was significantly lower than in ddY mice, significantly increased after sensitization. During the postictal period, however, it slowly decreased again and then gradually recovered to the preconvulsive level without any change in TRH receptor binding. In the striatum of El mice, although TRH receptor binding was significantly higher than in ddY mice, it was not affected by sensitization. These findings indicate that the hippocampal TRH system may play an inhibitory role in El mouse seizures whereas the striatal TRH system may be important for its seizure susceptibility.
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PMID:Changes in brain thyrotropin-releasing hormone (TRH) of seizure-prone El mice. 215 26

Recently, several systems of neuropeptides have been demonstrated to have anticonvulsant action in some forms of epilepsy to some extent. However, considerably less knowledge has been taken to their involvement in convulsive disorders either with regard to the development, expression or control of seizures. In this study, therefore, we examined the influence of amygdaloid kindling, an experimental model of temporal lobe epilepsy, on thyrotropin-releasing hormone (TRH), somatostatin (SS), cholecystokinin (CCK) and substance P (SP) content in the amygdala/piriform cortex and hippocampus. Male Sprague-Dawley rats were implanted bipolar electrodes into the left amygdala under pentobarbital anesthesia. Daily kindling stimulation was made to the left amygdala with 1 sec, 60 Hz, 400 microA, until 5 consecutive fully kindled generalized convulsive seizures were elicited. Subsequently, amygdaloid kindled rats were decapitated 30 min, 24 hrs, 48 hrs, 7 days and 21 days after the last amygdaloid stimulation, and the amygdala/piriform cortex and hippocampus were dissected. Control animals only received chronic electrodes, but no stimulation was delivered. The immunoreactivity of TRH, SS, CCK and SP was examined by methods of specific radioimmunoassay. The TRH content in these two brain regions significantly increased 24 hrs after the last kindled convulsion. This increase became maximal 48 hrs after the last convulsion: about 3-fold and 4-fold of the control in the amygdala/piriform cortex and hippocampus, respectively. Such increases in the TRH content tended to persist for 7 days, but returned to the control level 21 days after the last convulsion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of amygdaloid kindling on thyrotropin-releasing hormone, somatostatin, cholecystokinin and substance P contents of the amygdala/piriform cortex and hippocampus of rats]. 246 12

Various factors possibly influencing responsiveness to thyrotropin-releasing hormone (TRH) therapy were studied in 38 children (20 M, 18 F) with severe epilepsy. Mean age at treatment was 4.7 years (range; 0-18 years). Seizure type was infantile spasms (IS) in 16, generalized tonic seizures in 8, secondarily generalized partial seizures in 4, generalized tonic-clonic seizures in 2, atypical absence in 5, myoclonic seizures in 1, and atonic seizures in 2 cases. All seizure types were classified by ictal EEGs documented by simultaneous EEG-VTR according to the International Classification of seizures, except for two with atonic seizures and one with IS. Factors analyzed were sex, age, etiology, neurologic abnormality, seizure types, seizure frequency, EEGs, duration of TRH therapy, and serum hormone [human growth hormone (HGH), prolactin (PRL), thyroid-stimulating hormone (TSH)] levels before and after TRH therapy. We showed that: (a) serum PRL level was significantly correlated to effectiveness of TRH therapy (the higher the PRL, the greater the response rate); (b) serum basal PRL decreased significantly, especially in good responders; and (c) serum basal PRL was elevated especially in patients with IS, which responded more to TRH therapy. These interesting findings seen in severe epilepsy of childhood deserve further neuroendocrinologic study.
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PMID:Factors influencing effectiveness of thyrotropin-releasing hormone therapy for severe epilepsy in childhood: significance of serum prolactin levels. 249 23

Both thyrotropin-releasing hormone (TRH) and RO 15-4513 antagonize ethanol-induced depression, but this common property does not infer that both compounds share similar mechanisms of action. In the present studies, both TRH (30 mg/kg, i.p.) and RO 15-4513 (10 mg/kg, i.p.) reversed ethanol-induced depression of locomotor activity, in accord with previous reports. However, the benzodiazepine antagonist, RO 15-1788, blocked this action of RO 15-4513, while exerting no effect on the analeptic action of TRH. Using a model of seizure activity electrically elicited from the inferior colliculus, ethanol exerted a dose-related attenuation of seizure activity. This anticonvulsant action of ethanol was not altered by TRH (30 mg/kg, i.p.), but RO 15-4513 (3 mg/kg) reversed the effect of the 0.5, but not the 1.0 g/kg, dose of ethanol. In addition, pretreatment with RO 15-4513 (1 or 3 mg/kg, i.p.), but not TRH (30 mg/kg, i.p.), caused seizure generalization into the forebrain following inferior collicular stimulation, further verifying the proconvulsant properties of RO 15-4513. In conclusion, the analeptic action of TRH appears independent of benzodiazepine activity, and in contrast to RO 15-4513, TRH does not exhibit proconvulsant properties. Furthermore, because TRH did not antagonize both depressant actions of ethanol studied, it appears unlikely that TRH directly interacts with the molecular basis of ethanol action.
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PMID:Mechanistic and functional divergence between thyrotropin-releasing hormone and RO 15-4513 interactions with ethanol. 251 20

Neuropeptides represent a new class of compounds with important implications for the understanding of the mechanisms and treatment of epileptic disorders. Several systems of peptide modulators--in particular the opioid-like peptides, vasopressin, somatostatin, thyrotropin-releasing hormone (TRH) and ACTH--have partially demonstrated endogenous roles in some forms of epilepsy. Seizures and stressful situations may release endogenous opioid peptides and mediate postictal depression and postictal seizure refractoriness. Vasopressin is believed to increase susceptibility to convulsions and may be involved in the pathogenesis of febrile convulsions. Derangements in TRH regulation may lower thresholds for seizure expression by regulating arousal systems; however, some TRH analogs have proven to be effective anticonvulsants. Long-term alterations in somatostatin regulation could be components of focal epilepsies. ACTH is particularly useful in the treatment of infantile spasms. Pharmacological effects of these and other peptides have potentials for defining new classes of anticonvulsants. Cholecystokinin (CCK) and its analogs, the opioid peptides beta-endorphin and FK33824, TRH analogs, and several dipeptides exhibit potent anticonvulsant properties in chemical, electroshock, and genetic model screens. Convulsant actions of CRF, somatostatin, TRH, vasopressin, and high doses of endorphin or enkephalins may provide new tools to study regulatory mechanisms of cerebral excitability. The enkephalin epileptogenic effect is being developed as a predictive tool for new anti-petit mal anticonvulsants. Advances in molecular biology have identified the genes of particular peptide families. A concept has developed that the large propeptide precursors, coded by these genes, whose processing leads to functional peptide formation and release, regulate peptidergic humoral responses to external stimuli. This idea may have particular application in the understanding of the genetic basis of some seizure states. Techniques for amplification of mRNA expression have identified specific neuronal proteins and peptides. Knowledge of protein and propeptide structural cleavage sites has suggested previously unknown candidates for modular systems in epileptic states. Technological advances in automated peptide sequencing and synthesis have allowed the development of metabolically resistant analogs and antagonist peptides. The anticonvulsant potencies of CCK, TRH, and opioid peptides have been defined more clearly with these methods.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuropeptides: anticonvulsant and convulsant mechanisms in epileptic model systems and in humans. 287 23

In order to study the relationship between pentylenetetrazol (PTZ)-induced seizures and the thyrotropin-releasing hormone (TRH) neural system, immunoreactive TRH (IR-TRH) and TRH receptor binding activity were determined in discrete regions of the rat brain before as well as 40 s (immediately before seizures), 150 s (during seizures) and 24 h after an intraperitoneal injection of PTZ (75 mg/kg). IR-TRH markedly increased in the septum 40 and 150 s after the injection, and also in the hippocampus and the thalamus-midbrain region 40 and 150 s after the injection, respectively. However, no significant changes were observed in the TRH receptor binding before, during or after the seizures, suggesting that the increased IR-TRH was not released into the synaptic cleft. This speculation was supported by the dose-dependent inhibition of PTZ-induced generalized seizures by the pre-treatment with TRH or its analogue DN-1417 into the cerebral ventricle.
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PMID:Involvement of thyrotropin-releasing hormone (TRH) neural system of the brain in pentylenetetrazol-induced seizures. 300 43

We investigated the effects and side effects of thyrotropin-releasing hormone (TRH) on severely epileptic children to evaluate the clinical usefulness of TRH in the treatment of epilepsy and compared them with the results of ACTH therapy. The subjects were 64 patients admitted consecutively between 1980 and 1986. Their seizures were frequent, more than one a day or more than one a week. The subjects were divided into two groups; 33 patients treated with ACTH and 31 treated with TRH. The mean follow-up periods in TRH and ACTH therapy were 8 months and 3.0 years, respectively. The daily dose of TRH-t 0.5-1 mg was administered intravenously (i.v.) or intramuscularly (i.m.) for 1-4 weeks. The follow-up periods were 3-12 months (mean 6 months). In the TRH group, complete control of seizures was achieved in 7 of 13 (53.7%) of those with infantile spasms, and marked improvement of EEGs were observed in 8 of 13 (61.5%) of them. In the ACTH group, seizure cessation was observed in 75% of infantile spasms. Of the patients who received ACTH, 66.7% had various side effects, including pneumonia, huge subcutaneous abscess, hypokalemia, cataracts, and brain shrinkage as shown on computed tomography (CT), whereas only 16.7% of the patients treated with TRH had transient reduction of urine volume without other laboratory and physical abnormalities. The results of the study indicated that some patients who received TRH had cessation of infantile spasms and improved EEG findings with no serious side effect. Because of the untoward side effects of ACTH therapy, TRH is considered a possible new treatment for children with infantile spasms.
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PMID:Clinical effects of thyrotropin-releasing hormone for severe epilepsy in childhood: a comparative study with ACTH therapy. 302 59

We reported previously that DN-1417, a potent analog of thyrotropin-releasing hormone (TRH), suppressed both the progression of amygdaloid (AM) kindling and AM kindled seizure. To study a functional role of the cerebral TRH mechanism in AM kindling, immunoreactive TRH (IR-TRH) and specific TRH receptor binding were examined in the rat brains kindled from the left AM. The IR-TRH concentration elevated significantly in the amygdala plus piriform cortex and the hippocampus 24 and 48 hours after the AM kindled convulsion. Such an elevation of IR-TRH was not found 7 days after the last convulsion, indicating that the elevation of IR-TRH was a transient change seen after the AM kindled convulsion. By contrast, the specific TRH receptor binding in the striatum increased 48 hours, 7 and 21 days after the AM kindled convulsion. This indicates that the increase of the specific TRH binding in the striatum was a long-lasting change. The present study suggests that the change in the striatal TRH receptors may be associated with a long-lasting seizure susceptibility of AM kindled rats.
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PMID:Change in brain thyrotropin-releasing hormone (TRH) mechanism of amygdaloid kindled rats. 303 70

Our previous finding that intracerebroventricular (i.c.v.) administration of both thyrotropin-releasing hormone (TRH) and its analogue, gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate (DN-1417), suppressed seizure development of amygdaloid (AM) kindling and kindled AM seizures leads to a new hypothesis that endogenous TRH may be an antiepileptic substance in the brain. In this study, we examined postictal chronological changes in both immunoreactive TRH (IR-TRH) and TRH receptor binding activity in discrete brain regions of AM-kindled rats to study the relationship of the brain TRH system to kindling-induced seizure susceptibility. AM-kindled rats were decapitated 30 min, 24 h, 48 h, 7 days, and 21 days after the last kindled convulsion. IR-TRH increased markedly in the AM/pyriform cortex and hippocampus 24 and 48 h after the last convulsion, and returned to the control (unstimulated, sham-operated) value within 3 weeks after the convulsions ended. In contrast, a significant increase in the striatal TRH binding sites was evident 24 h after the cessation of convulsions which lasted 21 days. A lasting change in the striatal TRH neural system may be related to kindling-induced seizure susceptibility.
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PMID:Long-term increase in striatal thyrotropin-releasing hormone receptor binding caused by amygdaloid kindling. 303 60

We have previously demonstrated substantial increases in thyrotropin-releasing hormone (TRH) in specific regions of rat forebrain two days after single or repeated alternate-day electroconvulsive shock (ECS). To determine longer term effects of ECS-induced seizures on forebrain TRH content, we extended the time of the post-ECS observations to 6 and 12 days following 1 (ECS x 1) or 3 (ECS x 3) alternate-day ECS. Previous observations at 2 days post-ECS were confirmed except that hippocampal content of TRH was higher after ECS x 1. In pyriform cortex TRH remained elevated for 6 days after ECS x 1 and 3, and for 12 days after ECS x 3. In hippocampus TRH was elevated for 6 days after ECS x 1 and tended to remain elevated beyond 2 days after ECS x 3. In anterior cortex the increase persisted 6 days after ECS x 1 and 12 days after ECS x 3. These data show that convulsive seizures can induce sustained elevations of TRH beyond 48 h. This finding may be especially important in pyriform cortex and hippocampus where TRH may function as an endogenous anti-epileptic. Our data are also consistent with a possible role for TRH in affective regulation in the hippocampus, amygdala, pyriform and other cortical regions. Moreover, the present results further advance the analogy of the time-course of the TRH changes in rat to the course of the antidepressant response to electroconvulsive treatment in humans.
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PMID:The prolonged increase in thyrotropin-releasing hormone in rat limbic forebrain regions following electroconvulsive shock. 312 Feb 46


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