The Experts below are selected from a list of 180 Experts worldwide ranked by ideXlab platform
Yoshihiro Takeuchi - One of the best experts on this subject based on the ideXlab platform.
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Thyrotropin-Releasing Hormone (Protirelin)
CNS Drugs, 1996Co-Authors: Yoshihiro TakeuchiAbstract:Thyrotropin-Releasing Hormone (TRH; protirelin) is the smallest known peptide Hormone. It has central effects, unrelated to its endocrine effects, via an action at the pituitary-thyroid axis.
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Thyrotropin-Releasing Hormone in treatment of intractable epilepsy: Neurochemical analysis of CSF monoamine metabolites
Pediatric neurology, 1995Co-Authors: Yoshihiro Takeuchi, Akira Nishimura, Masashi Tominaga, Nobuto Mitsufuji, Ichiro Yamazoe, Syouji Kawase, Satoshi Matsuo, Tadashi SawadaAbstract: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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Efficacy of Thyrotropin-Releasing Hormone in the treatment of spinal muscular atrophy.
Journal of Child Neurology, 1994Co-Authors: Yoshihiro Takeuchi, Yuri Miyanomae, Yoshikazu Oomizono, Sozo Okano, Tetuo Nishiki, Hiroshi Komatsu, Akira Nishimura, Tadashi SawadaAbstract:Children with spinal muscular atrophy were treated by the administration of Thyrotropin-Releasing Hormone. In three infants with spinal muscular atrophy type I, Thyrotropin-Releasing Hormone showed little efficacy, but in children with types II and III, there was improvement in motor function and electromyographic findings after the Thyrotropin-Releasing Hormone therapy. Thyrotropin-Releasing Hormone has a neurotrophic effect on the spinal anterior motor neurons of spinal muscular atrophy patients and thus may be warranted for the management of spinal muscular atrophy. (J Child Neurol 1994;9:287-289).
M.j Kubek - One of the best experts on this subject based on the ideXlab platform.
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Increases in Thyrotropin-Releasing Hormone messenger RNA expression induced by a model of human temporal lobe epilepsy: effect of partial and complete kindling
Neuroscience, 1997Co-Authors: S.m Knoblach, M.j KubekAbstract:Abstract 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-μA stimulation of the amygdala was not associated with accumulation of Thyrotropin-Releasing Hormone messenger RNA. Thus, only fully 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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Changes in Thyrotropin-Releasing Hormone levels in hippocampal subregions induced by a model of human temporal lobe epilepsy: effect of partial and complete kindling
Neuroscience, 1997Co-Authors: S.m Knoblach, M.j KubekAbstract:Abstract 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 144 h. 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.
Robert M. Post - One of the best experts on this subject based on the ideXlab platform.
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Effects of Intrathecal Thyrotropin-Releasing Hormone (Protirelin) in Refractory Depressed Patients
Archives of general psychiatry, 1997Co-Authors: Lauren B. Marangell, Mark S. George, Ann M. Callahan, Terence A. Ketter, Peggy J. Pazzaglia, Todd L'herrou, Gabriele S. Leverich, Robert M. PostAbstract:Background: Therapeutic effects of the tripeptide protirelin (Thyrotropin-Releasing Hormone) have been postulated in the affective disorders, but direct assessment in humans has been hindered by poor blood-brain barrier permeability. Methods: Eight medication-free inpatients with refractory depression received 500 μg of protirelin via a lumbar intrathecal injection and an identical sham lumbar puncture procedure, separated by 1 week, in a doubleblind crossover design. Results: Five of eight patients responded to intrathecal protirelin, defined as a 50% or greater reduction in an abbreviated Hamilton Rating Scale for Depression score. Suicidality also was reduced significantly (P Conclusion: Administration of protirelin by an intrathecal route induced a rapid improvement in mood and suicidality in these refractory depressed patients, supporting the hypothesis that Thyrotropin-Releasing Hormone could be a positive modulator of mood.
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Carbamazepine Increases Cerebrospinal Fluid Thyrotropin-Releasing Hormone Levels in Affectively Ill Patients
Archives of general psychiatry, 1994Co-Authors: Lauren B. Marangell, Mark S. George, Peggy J. Pazzaglia, Garth Bissette, Teresa Huggins, Robert M. PostAbstract:Background: Thyrotropin-Releasing Hormone is an endogenous tripeptide with endocrine-independent neurophysiologic properties that may be relevant to affective or seizure disorders. We studied the effect of carbamazepine, which has both mood-stabilizing and anticonvulsant properties, on cerebrospinal fluid Thyrotropin-Releasing Hormone levels in affectively ill patients. Method: Paired cerebrospinal fluid samples were collected from nine inpatients with mood disorders, both while medication free and while taking carbamazepine for an average of longer than 1 month at 950 mg/d, achieving blood levels of 8.8 mg/L. Results: Carbamazepine treatment was consistently and significantly associated with increased cerebrospinal fluid Thyrotropin-Releasing Hormone levels (P Conclusion: As carbamazepine-induced increases in Thyrotropin-Releasing Hormone levels could be relevant to either its psychotropic or anticonvulsant properties, further clinical and preclinical investigation of this finding appears indicated.
W. Lason - One of the best experts on this subject based on the ideXlab platform.
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Effects of pentylenetetrazole-induced kindling on Thyrotropin-Releasing Hormone biosynthesis and receptors in rat brain.
Neuroscience, 1999Co-Authors: Lucylla Jaworska-feil, J Turchan, Barbara Przewlocka, B. Budziszewska, Monika Leśkiewicz, W. LasonAbstract:Abstract It has been postulated that changes in Thyrotropin-Releasing Hormone biosynthesis may be involved in the mechanism of kindling—an animal model of epileptogenesis. To test this hypothesis, a time-course study was carried out to investigate the effects of pentylenetetrazole kindling (40 mg/kg i.p., daily for eight days) on the expression of gene coding for preproThyrotropin-Releasing Hormone, the Thyrotropin-Releasing Hormone tissue level and Thyrotropin-Releasing Hormone receptor parameters in rat brain. As shown by an in situ hybridization study, a single, convulsant dose of pentylenetetrazole (70 mg/kg i.p.) increased the preproThyrotropin-Releasing Hormone messenger RNA level in the dentate gyrus of the hippocampal formation and pyriform cortex after 3 h and, to a greater extent, after 24 h. Those changes were accompanied with increases in the Thyrotropin-Releasing Hormone level in the striatum, hippocampus, amygdala and piriform cortex. Seven days after single pentylenetetrazole administration, the Thyrotropin-Releasing Hormone level was still significantly elevated in the piriform cortex and striatum. Acute pentylenetetrazole decreased the density (Bmax) of Thyrotropin-Releasing Hormone receptors in the striatum after 3 and 24 h, and increased that density in the piriform cortex and amygdala after 24 h and seven days, respectively. The Thyrotropin-Releasing Hormone receptor affinity (Kd) was decreased in the striatum and increased in the amygdala after only 3 h. Kindled rats showed a moderate increase in the preproThyrotropin-Releasing Hormone messenger RNA content in the dentate gyrus of the hippocampal formation and piriform cortex after 3 and 24 h; however, a significant decrease in those parameters was found after 14 days. After 3 and 24 h, pentylenetetrazole kindling also elevated the Thyrotropin-Releasing Hormone content in the hippocampus, piriform cortex, and striatum (in the latter structure after 24 h only), whereas in the septum the Thyrotropin-Releasing Hormone level was decreased. After seven days, the Thyrotropin-Releasing Hormone level was still elevated in the hippocampus and piriform cortex of kindled rats, but after 14 days it was significantly lowered in the hippocampus. The kindled rats also showed a significant decrease in the density (Bmax) of Thyrotropin-Releasing Hormone receptors in the striatum (after 24 h, seven and 14 days), and an increase in the piriform cortex (after seven days). The Thyrotropin-Releasing Hormone receptor affinity (Kd) value was increased in the hippocampus after seven and 14 days, and in the piriform cortex after seven days. These results indicate that pentylenetetrazole kindling induces long-lasting alterations in the Thyrotropin-Releasing Hormone biosynthesis and Thyrotropin-Releasing Hormone receptor affinity in discrete regions of rat brain. These region-specific changes, in particular down-regulation of the Thyrotropin-Releasing Hormone biosynthesis in the hippocampus, may be involved in chronic neuronal hyperexcitability associated with kindling.
S.m Knoblach - One of the best experts on this subject based on the ideXlab platform.
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Increases in Thyrotropin-Releasing Hormone messenger RNA expression induced by a model of human temporal lobe epilepsy: effect of partial and complete kindling
Neuroscience, 1997Co-Authors: S.m Knoblach, M.j KubekAbstract:Abstract 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-μA stimulation of the amygdala was not associated with accumulation of Thyrotropin-Releasing Hormone messenger RNA. Thus, only fully 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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Changes in Thyrotropin-Releasing Hormone levels in hippocampal subregions induced by a model of human temporal lobe epilepsy: effect of partial and complete kindling
Neuroscience, 1997Co-Authors: S.m Knoblach, M.j KubekAbstract:Abstract 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 144 h. 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.