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

This paper reviews chemical models of epilepsy and their relevance in the identification and characterization of anticonvulsants. For each convulsant we discuss possible modes of administration, clinical type(s) of seizures induced, proposed mechanism(s) of epileptogenesis and, where available, responsiveness of the induced seizures to anticonvulsants. The following compounds are reviewed: pentylenetetrazol, bicuculline, penicillin, picrotoxin, beta-carbolines, 3-mercaptopropionic acid, hydrazides, allylglycine; the glycine antagonist strychnine; gamma-hydroxybutyrate; excitatory amino acids (glutamate, aspartate, N-methyl-D-aspartate, quisqualate, kainate, quinolinic acid); monosubstituted guanidino compounds, metals (alumina, cobalt, zinc, iron); neuropeptides (opioid peptides, corticotropin releasing factor, somatostatin, vasopressin); cholinergic agents (acetylcholine, acetylcholinesterase inhibitors, pilocarpine); tetanus toxin; flurothyl; folates; homocysteine and colchicine. Although there are a multitude of chemical models of epilepsy, only a limited number are applied in the routine screening of potential anticonvulsants. Some chemical models have a predictive value with regard to the clinical profile of efficacy of the tested anticonvulsants. Some chemical models may contribute to a better understanding of possible mechanisms of epileptogenesis.
 ...
PMID:Chemical models of epilepsy with some reference to their applicability in the development of anticonvulsants. 139 44

The neuroanatomical substrate of seizures induced by picomolar amounts of corticotropin-releasing hormone in infant rats was investigated. Electrographic and behavioral phenomena were monitored in 42 rat pups aged 5 to 22 days. Rat pups carried bipolar electrodes implanted in subcortical limbic structures, as well as cortical electrodes and intracerebroventricular cannulae. The administration of corticotropin-releasing hormone produced age-specific seizures within minutes, which correlated with rhythmic amygdala discharges. Paroxysmal hippocampal and cortical discharges developed subsequently in some rats. Corticotropin-releasing hormone-induced electrographic and behavioral seizures originate in the amygdala.
 ...
PMID:Corticotropin-releasing hormone-induced seizures in infant rats originate in the amygdala. 159 84

Corticotropin-releasing factor (CRF) injected into the cerebral ventricles of small mammals induces EEG limbic seizures, behavioral excitability, stereotyped behavior, and tardive enhancement of hippocampal theta voltage and frequency. Because we addressed this phenomenon when we explained the pathogenesis of infantile spasms in children, we wished to study the interference exerted by some gamma-endorphin fragments on EEG epileptiform and behavioral symptoms induced by CRF in the rabbit. Animals were implanted intracerebroventricularly (i.c.v.) with semichronic cortical and hippocampal electrodes, together with a cannula into the left lateral ventricle. When some gamma-endorphin derivatives (DT gamma E, DE gamma E) were injected intravenously (i.v.) for 4 days (or hydrocortisone once), they prevented the EEG ictal seizures induced in the hippocampus of rabbits by CRF injected i.c.v. Hydrocortisone and DE gamma E also prevented the appearance of scattered spiking and partially prevented tardive enhancement of theta voltage in the hippocampal EEG. Finally, DE gamma E also prevented stereotyped behavior and excitability induced by CRF. These results confirm the regulatory role exerted by CRF in limbic structure excitability and suggest that the above peptides may be involved in a regulatory feedback mechanism of CRF metabolism or activity. The possibility that these peptides may also have interesting antiepileptogenic properties should be considered.
 ...
PMID:Some endorphin derivatives and hydrocortisone prevent EEG limbic seizures induced by corticotropin-releasing factor in rabbits. 170 Sep 51

Expression of the proto-oncogene c-fos is known to increase in rat brain following various types of seizures. Measuring c-fos mRNA or protein levels was shown to be a good cellular marker for neurons activated during central nervous system (CNS) excitation. In this study, we used in situ hybridization analysis of c-fos mRNA to determine brain regions activated by a peptide that has been closely linked to stress responsivity and kindling-like seizure activity. Corticotropin-releasing hormone (CRH) was injected into the left lateral ventricle of rats and produced the late onset of seizures between 1.5-5 h after its administration. Rats were sacrificed at various time points after the administration of CRH or sterile water, and c-fos mRNA levels were determined. In the preseizure state, CRH increased c-fos unilaterally in several cerebral cortical structures (most prominently in the dorsal endopiriform nucleus and in the piriform and insular cortices). CRH-induced seizures increased c-fos bilaterally in the same cortical regions, and in addition, in the hippocampus and olfactory bulb. The data are congruous with the hypothesis that intracerebroventricularly (i.c.v.) administered CRH elicits a rapid kindling-like response.
 ...
PMID:Expression of c-fos mRNA in rat brain after intracerebroventricular administration of corticotropin-releasing hormone. 178 25

Corticotropin-releasing hormone (CRH) administered into the cerebral ventricles of rats during the first postnatal week caused a specific and stereotyped behavior sequence: rhythmic chewing and licking (jaw myoclonus) were followed by 'limbic'-type seizures. The onset of the seizures was much more rapid (2-45 min vs 3-7 h) than in adult rats, and the convulsant doses were much lower (50 x 10(-12) mol per gram brain weight vs 750 x 10(-12) mol per gram brain weight in adults). CRH potency in inducing seizures varied inversely with age. CRH-induced seizures occurred prior to any changes in serum corticosterone, and were eliminated by the administration of a CRH antagonist, as well as of phenytoin. Electrocorticographic correlates of CRH-induced behaviors in the infant rat were inconsistent, suggesting a subcortical origin of CRH-induced paroxysmal events in the immature brain.
 ...
PMID:Corticotropin-releasing hormone is a rapid and potent convulsant in the infant rat. 191 60

A cholinergic projection from the dorsolateral tegmentum to the medial anterior cortex has previously been shown to contain substance P and corticotropin releasing factor. Behavioral analysis of acetylcholine, substance P and corticotropin releasing factor microinjected into the medial anterior cortex revealed a seizure-related "boxing" behavior elicited by carbachol, which was potentiated by coinjection with substance P and antagonized by coinjection with corticotropin releasing factor. We now report that two antagonists of substance P receptors, [D-Pro2, D-Phe7, D-Trp9]-substance P and [D-Pro2, D-Trp7,9]-substance P, attenuate "boxing" behavior when coinjected with carbachol. Neither antagonist produced observable behavioral effects when microinjected alone. An analog of substance P, [pGlu,5, MePhe,8 Sar9]-substance P (5-11) potentiated carbachol-induced "boxing" at doses similar to naturally-occurring substance P. Monoclonal and polyclonal antisera against substance P were not effective antagonists of carbachol-induced "boxing." The ability of substance P antagonists to block carbachol-induced "boxing" has two major implications: (1) endogenous substance P may be modulating endogenous acetylcholine in the tegmental-cortical pathway; and (2) substance P antagonists may provide a new avenue for the development of antiepileptic drugs.
 ...
PMID:Substance P antagonists block carbachol-induced "boxing" behavior at a site of coexistence in the rat prefrontal cortex. 248 49

The effects of repeated electroconvulsive seizures (ECS) on expression of mRNAs coding for corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical (HPA) axis and hypothalamo-neurohypophysial system (HNS) were assessed via semi-quantitative in situ hybridization histochemical analysis. Measures of mRNA content were accompanied by measurement of peptide- and hormone-expression in the relevant neuroendocrine systems. Following 7 daily ECS treatments, CRF mRNA was significantly increased in the medial parvocellular paraventricular nucleus (PVN) of treated rats relative to controls. CRF peptide content of whole PVN homogenates was decreased to 50% of control levels. Changes in CRF message and peptide levels were accompanied by increases in pituitary ACTH content and by elevated plasma corticosterone, suggesting ECS elicits long-term up-regulation of the HPA axis. AVP mRNA in the medial parvocellular PVN, which is known to up-regulate in response to HPA challenge by adrenalectomy, was not increased by ECS. Chronic ECS causes a clear up-regulation of HNS neurons of the supraoptic nucleus, characterized by increased AVP mRNA content, decreased AVP peptide content, and depletion of neurohypophysial AVP. However, no changes were observed in magnocellular vasopressinergic neurons of the PVN, indicating that magnocellular SON and PVN neurons respond differentially to stimulation by ECS. The data indicate that ECS is a potent stimulus for activation of select components of both the HPA axis and the HNS. As such, ECS provides a useful tool for examining mechanisms underlying neuroendocrine processes.
 ...
PMID:Chronic electroconvulsive shock treatment elicits up-regulation of CRF and AVP mRNA in select populations of neuroendocrine neurons. 281 39

Two cases of hypothalamic hamartoma are presented. The first patient was a 4-year-old boy with precocious puberty, and the second was a 6-year-old boy with epileptic seizures. In both patients, clinical symptoms and signs appeared at the age of 2 years and progressed thereafter. Computerized tomography and magnetic resonance imaging in both cases disclosed a suprasellar mass lesion in continuity with the hypothalamus. Removal of the lesions affected the endocrinological status and/or seizure control. Pathological examination revealed the lesions to be composed of well-differentiated neuronal and glial cells. Immunohistochemical study demonstrated the presence of beta-endorphin, corticotropin-releasing factor, oxytocin, and neurofilament protein (210 kD) in the neuronal cells of the first patient, but no neuropeptides were detected in the second. Electron microscopic examination on the second patient disclosed the presence of many nonmyelinated and some myelinated neuronal processes containing dense-core and clear vesicles. The morphological characteristics and the role of surgery for this lesion are discussed.
 ...
PMID:Hypothalamic hamartoma. Report of two cases. 292 5

High amplitude spiking representative of seizures, accompanied by an unusual motor behavior pattern of rearing and forelimbic clonus resembling "boxing," was elicited by microinjection of the cholinergic agonist, carbachol, 4 micrograms, into the medial prefrontal cortex of the rat. A rating scale devised to score the behavior revealed a motor pattern elicited by carbachol from the medial anterior cortex which was similar to that described by Racine for electrical stimulation of the amygdala. Topographical analysis of the areas surrounding the medial anterior cortex region revealed that the motor manifestations of seizures were elicited over a wide region of the anterior cortex, with scores significantly lower at carbachol microinjection sites greater than 1 mm rostral, 2 and 3 mm caudal, and 2 mm lateral to the standard medial prefrontal cortex site. Unilateral microinjection of carbachol yielded motor seizures primarily from the contralateral forepaw, suggesting involvement of a crossed pathway. Retrograde tracing with fast blue dye, combined with immunostaining for choline acetyltransferase and NADPH-diaphorase, found that the cholinergic neurons innervating the standard microinjection site were the dorsolateral tegmental cells, as previously reported, which have been shown to also contain substance P and corticotropin releasing factor. In addition, cholinergic neurons of the nucleus basalis of Meynert region were found to innervate the standard microinjection site. These findings implicate cholinergic innervation of the rostral cortex in classical limbic seizures.
 ...
PMID:Anatomical analysis of frontal cortex sites at which carbachol induces motor seizures in the rat. 317 34

Intracerebroventricular (i.c.v.) administration of ovine corticotropin-releasing factor (CRF) in doses varying from 10 to 100 micrograms has been reported to produce the late onset of seizures that resemble those observed during electrical kindling of the amygdala. We assessed the effects of repeated CRF administration on seizure development and on subsequent electrical kindling of the amygdala. Rats were administered vehicle or CRF (100 micrograms in 10 microliter of sterile water, i.c.v.) once daily for 5 consecutive days and were rated for seizures and aggressive behavior. On days 1 or 2, all animals receiving CRF developed major motor seizures of late onset (1-5 h post-injection), accompanied by spiking in the amygdala. By day 5, however, no rats had seizures, suggesting the development of tolerance. Defensive biting attacks were also observed following latencies of several hours and tolerance appeared to develop to these as well. After the CRF regimen, treated rats developed amygdala-kindled seizures following electrical stimulation approximately twice as fast as vehicle-injected controls (P less than 0.03). In a second experiment, rats were electrically kindled or sham-kindled prior to receiving i.c.v. CRF (100 micrograms). Kindled animals were significantly less sensitive to the seizure-inducing effects of CRF (P less than 0.03), but were more intensely aggressive than sham-kindled animals or naive rats receiving CRF for the first time.
 ...
PMID:CRF-induced seizures and behavior: interaction with amygdala kindling. 348 94


1 2 3 4 5 Next >>