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

Several of the non-sex hormones have been found to be useful in the treatment of seizures. These hormones have an effect on seizures, and seizures have an effect on these hormones. Adrenocorticotropic hormone (ACTH) and corticosteroid drugs have been found to be useful in the treatment of infantile spasms and other seizure disorders. Unfortunately, there is no clear consensus regarding superiority of ACTH versus prednisone in regard to efficacy and long-term benefits, dosage, or duration of treatment. There is also considerable debate regarding reasons why ACTH and prednisone are useful in infantile spasms, their mechanism of action, and their long-term effects on brain development. Thyrotropin-releasing hormone also has been used in the treatment of infantile spasms and other seizure types in children, with modest success. As with ACTH and prednisone, the mechanisms of action remain unclear.
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PMID:Effect of non-sex hormones on neuronal excitability, seizures, and the electroencephalogram. 165 81

The efficacy of thyrotropin-releasing hormone in children with intractable epilepsy was investigated and changes in cerebrospinal fluid monoamine metabolites were analyzed. The 18 patients had either West syndrome (12 patients) or Lennox-Gastaut syndrome (6 patients), which was intractable to antiepileptic drug therapy and to adrenocorticotrophic hormone. Thyrotropin-releasing hormone-tartrate was administered for 4 weeks. Before and after the thyrotropin-releasing hormone administration, cerebrospinal fluid was collected and analyzed for 5-hydroxyindoleacetic acid, kynurenine, homovanillic acid, and 3-methoxy-4-hydroxyphenyl glycol. The patients were classified into 3 groups, based on seizure frequency and electroencephalographic effects: cessation of seizures and seizure discharges (very effective; group A), reduction of seizures and/or seizure discharges (effective; group B), and no changes in frequency of seizures or discharges (not effective; group C). There were 6 patients in group A, 3 in group B, and 9 in group C. There were no significant differences in monoamine metabolites before and after the thyrotropin-releasing hormone therapy. A trial of thyrotropin-releasing hormone for the treatment of intractable epilepsy is warranted and further study is required on the mechanism of the antiepileptic action of thyrotropin-releasing hormone.
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PMID:Thyrotropin-releasing hormone in treatment of intractable epilepsy: neurochemical analysis of CSF monoamine metabolites. 754 12

Thyrotropin-releasing hormone (TRH) has been found to be widely distributed in the mammalian central nervous system. Further, the concentration of the tripeptide increases following seizure activity, and TRH is known to have anticonvulsant effects. We have investigated the possibility that the anticonvulsant activity of TRH may be due, at least in part, to an attenuation of the glutamate-stimulated increases in intraneuronal Ca2+ ([Ca]i) that occur with epileptic activity. We find that the tripeptide does not itself excite neurons and that it is able to significantly reduce glutamate-stimulated increases in [Ca]i in cultured neurons derived from fetal rat forebrain. Increases in the concentration of TRH following seizure activity may represent an endogenous homeostatic mechanism for reducing glutamate-induced elevations in intraneuronal Ca2+.
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PMID:Thyrotropin-releasing hormone (TRH) attenuates glutamate-stimulated increases in calcium in primary neuronal cultures. 888 98

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

Thyrotropin-releasing hormone (TRH; Protirelin) is an endogenous neuropeptide known to have anticonvulsant effects in several seizure models and in intractable epileptic patients. Like most neuropeptides, its duration of action may be limited by a lack of sustained site-specific bioavailability. To attempt to provide long-term delivery, we attached TRH to a biodegradable polyanhydride copolymer as a sustained-release carrier. Utilizing the rat kindling model of temporal lobe epilepsy, a single TRH microdisk implanted stereotaxically into the seizure focus (amygdala) significantly suppressed kindling expression when assessed by the number of stimulations required to reach each behavioral stage and to become fully kindled (8.63 +/- 0.92 vs. 16.17 +/- 1.37; Mean +/- S.E.M.). Two indices of seizure severity, afterdischarge duration (Mean +/- S.E.M., sec.) (stimulated amygdala [87.40 +/- 5.47 vs. 51.80 +/- 15.65] and unstimulated amygdala [89.60 +/- 5.55 vs. 48.67 +/- 15.8] and clonus duration (71.2 +/- 5.94 vs. 29.40 +/- 8.87; Mean +/- S.E.M., sec.), were also significantly reduced by a single polymeric-TRH implant. Fifty days after initiation of the study a significant reduction in clonus duration (53.90 +/- 3.27 vs. 40.09 +/- 4.14) still remained in the TRH-implanted groups. This report is the first to provide evidence in support of in situ microdisk pharmacotherapy for potential neuropeptide delivery in intractable epilepsy and possibly other neurological disorders.
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PMID:Prolonged seizure suppression by a single implantable polymeric-TRH microdisk preparation. 985 10

Thyrotropin-releasing hormone (TRH) has been postulated to be involved in the regulation of seizures and neural degeneration. We examined the effects of TRH and its stable analogue, RGH-2202, on the kainate-induced seizures and excitotoxicity in mice - a model of a drug-resistant temporal lobe epilepsy. We found that TRH (2.0 and 5.0 mg/kg) and RGH-2202 (2.5 and 5 mg/kg) elevated the ED(50) for kainate-induced convulsions and tended to decrease mortality. A histological analysis showed that kainate caused a neuronal loss of CA(1) and CA(3) hippocampal fields. TRH (10, 20 and 50 mg/kg) and RGH-2202 (2.5, 7.5 and 10.0 mg/kg) markedly reduced the excitotoxic effect of kainate. Further studies showed that TRH (1-100 microM) and RGH-2202 (100 microM) significantly attenuated the kainate (150 microM)-induced lactate dehydrogenase release in a primary cortical cell culture from rat embryos. In conclusion, the present study showed that TRH and RGH-2202 attenuated the kainate-induced seizures and inhibited the kainate-evoked neurotoxicity in vivo and in vitro. These results support the hypothesis of a potential utility of TRH and its analogues in the treatment of seizures and some neurodegenerative diseases.
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PMID:Protective effects of TRH and its stable analogue, RGH-2202, on kainate-induced seizures and neurotoxicity in rodents. 1113 88

Intractable seizures remain a significant therapeutic challenge despite current advances in the treatment of epilepsy. Thyrotropin-releasing hormone, the first neuroendocrine releasing factor to be isolated and fully characterized, was also the first releasing factor investigated as a possible neurotransmitter/neuromodulator outside the hypothalamus. Basic and clinical research has revealed a distinct neuroanatomic distribution and a neurochemical role for thyrotropin-releasing hormone in seizure modulation. Thyrotropin-releasing hormone and selected analogs were reported to have antiepileptic effects in several animal seizure paradigms, including kindling and electroconvulsive shock. Clinically, thyrotropin-releasing hormone treatment has been reported to be efficacious in such intractable epilepsies as infantile spasms, Lennox-Gastaut syndrome, myoclonic seizures, and other generalized and refractory partial seizures. Herein, we review evidence that suggests that thyrotropin-releasing hormone and selected thyrotropin-releasing hormone analogs may represent a new class of novel antiepileptic drugs, namely, antiepileptic neuropeptides and provide insights into potential new treatments for the intractable epilepsies.
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PMID:Thyrotropin-releasing hormone in the treatment of intractable epilepsy. 1181 29

A patient with Williams syndrome, craniosynostosis, and infantile spasms is described. At age 6 months, the infant demonstrated infantile spasms and craniosynostosis and was operated on for craniosynostosis and treated with adrenocorticotropic hormone (ACTH) for the infantile spasms. ACTH completely controlled the seizures, but was halted because of the progression of ventricular hypertrophy. The seizure returned, and he was found to have elfin face, failure-to-thrive, developmental delay, and dental malformation in addition to congenital heart defects. High-resolution chromosome analysis revealed interstitial deletion of 7q11.22-q11.23. Therefore his clinical and cytogenetic diagnosis was Williams syndrome. Thyrotropin-releasing hormone (TRH) therapy reduced his seizures and improved the findings of EEG without cardiac side effects. In addition, his psychomotor development was slightly improved.
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PMID:Infantile spasms in a patient with williams syndrome and craniosynostosis. 1463 57

Excess excitatory amino acid release is involved in pathways associated with seizures and neurodegeneration. Thyrotropin-releasing hormone (TRH; protirelin), a brain-derived tripeptide, has shown efficacy in the treatment of such disorders, yet its mechanism of neuroprotection is poorly understood. Using superfused hippocampal slices, we tested the hypothesis that TRH could inhibit evoked glutamate/aspartate release in vitro. Rat hippocampal slices were first equilibrated in oxygenated Krebs buffer (KRB) (120 min) then superfused for 10 min with KRB (control), or KRB containing 0.1, 1, or 10 microM TRH respectively, prior to and during 5 min depolarization with high potassium KRB (50 mM [K(+)] +/- TRH). Fractions (1 min) were collected during the 5 min stimulation and for an additional 10 min thereafter and analyzed for glutamate and aspartate by HPLC. TRH had no effect on baseline glutamate/aspartate release, while all three TRH doses significantly (P < 0.05) inhibited peak 50 mM [K(+)]-stimulated glutamate/aspartate release, and glutamate remained below control (P < 0.05) at 15 min post stimulation. A 5 min pulse of TRH (10 microM) had no affect on basal glutamate/aspartate release, whereas the TRH pre-pulsed slices failed to release glutamate/aspartate by [K(+)]-stimulation given 15 min later. These results are the first to show a potent and prolonged inhibitory effect of TRH on evoked glutamate/aspartate release in vitro. These initial studies suggest that exogenous and/or endogenous TRH may function, in part, to modulate excess glutamate release in specific CNS loci. Additional studies are in progress to fully understand the mechanism of this potent effect of TRH and its implication in various CNS disorders.
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PMID:Thyrotropin-releasing hormone (protirelin) inhibits potassium-stimulated glutamate and aspartate release from hippocampal slices in vitro. 1605 93


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