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

The present study examined changes in mRNA expression of various neuropeptides at several stages of amygdala kindled seizures. 35S-labelled oligonucleotide probes for mRNA of enkephalin (ENK), dynorphin (DYN) and thyrotropin releasing hormone (TRH) were hybridized to brain sections of rats sacrificed 24 h after a stage 1 or stage 5 seizure, or 2 weeks after a stage 5 seizure. Changes in expression developed as kindling progressed, with long-lasting changes in ENK and transient changes in DYN and TRH. ENK mRNA levels increased in pyriform and entorhinal cortices at stage 1 and 5 and remained elevated in the pyriform two weeks after a stage 5 seizure. In contrast, DYN mRNA was decreased bilaterally in the dentate gyrus 24 h after a stage 5 seizure, but returned to control levels two weeks after a stage 5 seizure. TRH mRNA was dramatically increased 24 h after a stage 1 or stage 5 seizure. After a stage 1 seizure two patterns developed. One showed increases in the pyriform, entorhinal and perirhinal cortices ipsilateral to the stimulation. The other pattern displayed bilateral increases in the dentate gyrus with or without the unilateral increases the limbic cortices. Twenty-four hours after a stage 5 seizure, large bilateral increases were found in these areas, but these returned to baseline levels by two weeks after a stage 5 seizure. The data demonstrate a constellation of alterations in several peptide systems with distinct spatiotemporal patterns, particularly in regions known to be important in kindling and epilepsy, such as the dentate gyrus and pyriform and entorhinal cortices. The relationship of these neuropeptide mRNA changes to those previously found in c-fos mRNA expression during the development of kindling is discussed.
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PMID:Alterations in mRNA of enkephalin, dynorphin and thyrotropin releasing hormone during amygdala kindling: an in situ hybridization study. 135 74

We have employed a molecular biological approach to study the dynamic status of hippocampal opioid peptides in response to seizures elicited by different experimental models, such as electroconvulsive shocks (ECS) and amygdaloid kindling. Both ECS- and kindling-induced seizures triggered an initial large release of enkephalin and dynorphin, but produced opposite long-term effects on the biosynthesis of these two peptides, an increase of enkephalin, and a drastic decrease of dynorphin. Electrical stimulation of the perforant pathway produced differential changes of enkephalin and dynorphin, which were identical to those of ECS and kindling. This finding confirmed our hypothesis that the perforant pathway was responsible for the mediation of ECS- and kindling-induced changes in opioid peptide turnover. Strongest evidence indicating a role for opioid peptides in mediating the expression of seizure-related behaviors was found using the kainic acid model, where we saw that hippocampal enkephalin was essential to the expression of kainic acid-induced wet dog shakes (a preconvulsive shaking behavior). Furthermore, it was found that the granular-mossy fiber pathway of the ventral, but not the dorsal, hippocampus was essential for the expression of this shaking behavior. However, destruction of the granular-mossy fiber pathway potentiated the seizures and hippocampal cell loss induced by kainic acid. This unexpected, yet extremely interesting, finding not only distinguished the roles of the granular-mossy fiber pathway in mediating wet dog shakes vs. convulsive seizures, but also challenged the dogma that this granular-mossy fiber pathway is essential for the expression of limbic seizures.
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PMID:Hippocampal opioid peptides and seizures. 136 30

Patients with medically intractable temporal lobe epilepsy (TLE) undergo medial temporal lobectomy with hippocampectomy for one of two reasons. (1) A lesion (tumor or arteriovenous malformation) adjacent to, but not invasive of, the hippocampus, results in the removal of the lesion and adjacent hippocampus in order to ensure a tumor-free margin. This group will be referred to as tumor-related TLE (TTLE) patients. (2) The operation is performed when depth electrode recordings and other evaluative techniques point to the hippocampus as the focus of seizure initiation. This group will be referred to as cryptogenic TLE (CTLE) patients. Analysis of the hippocampi of these two groups of patients reveals that the TTLE hippocampus is quite similar to that of autopsy subjects in its chemical neuroanatomy. However, the dentate gyrus of the CTLE patients shows considerable morphological and cytochemical reorganization. This reorganization is characterized by a number of features. (1) There is a loss of granule cells which occurs either as a patchy loss and/or a thinning of the granule cell layer. (2) Remaining granule cells which contain dynorphin appear to produce recurrent collaterals into the inner molecular layer of the dentate gyrus. (3) In the subgranular region of the hilus (the polymorphic layer) there is a selective loss of interneurons immunoreactive for somatostatin, neuropeptide Y and substance P. (4) There appears to be an increase in fibers immunoreactive for somatostatin and neuropeptide Y which extend throughout the dentate molecular layer. Somatostatin fibers being less numerous than neuropeptide Y fibers (5). The distributions of a number of neurotransmitter receptors also show striking reorganization in the dentate gyrus of the CTLE hippocampus. (6) Second messenger systems protein kinase C and adenylate cyclase, and Na+, K(+)-ATPase activity, as determined by ouabain binding, is increased in the molecular layer of CTLE. This remodeling of the CTLE hippocampus may hold the key to the mechanisms of hyperexcitability of the granule cells in the hippocampus of this group, and consequently the generation of seizures. The removal of the hippocampus in CTLE patients results in good control of seizures, whereas removal of hippocampi that do not show such reorganization, in a group of patients classified as atypical CTLE patients, results in inadequate seizure control. These findings suggest a complex series of processes in converting the properly regulated granule cells into hyperexcitable ones.
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PMID:Neurotransmitters and their receptors in human temporal lobe epilepsy. 136 31

Multiple morphological and neurochemical changes are found in the dentate gyrus of humans with temporal lobe epilepsy (TLE). Three basically different types of changes will be discussed and some interrelationships considered. Neuronal loss in several regions of the hippocampal formation in human TLE has been recognized for many years, but only recently have the polymorph or hilar neurons been evaluated as a distinct group of neurons, and cell loss in this region is now being documented in many cases with severe TLE. Reorganization of afferents within the molecular layer of the dentate gyrus is also found in a high percentage of TLE specimens. The apparent reorganization of mossy fibers from the dentate granule cells is particularly striking, and aberrant innervation of the inner part of the molecular layer by zinc- and dynorphin-containing mossy fibers has been reported in human tissue by several groups of investigators. In a subpopulation of TLE specimens, there is also disorganization of the granule cell layer. Rather than being arranged in the compact, highly organized layer that is characteristic of control tissue, the granule cell bodies in some TLE cases are dispersed. In some additional cases, a bilaminar pattern of granule cells is observed. Each of these changes could contribute to altered circuitry within the dentate gyrus of humans with TLE, and such alterations could influence seizure susceptibility within the hippocampal formation.
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PMID:Morphological changes in the dentate gyrus in human temporal lobe epilepsy. 146 68

It was shown in the experiments on rats that the repeated picrotoxin administration resulted in the kindling of generalized seizures. Generalized convulsions were followed by the development of either postictal depression or explosiveness. The injection of mu-opiate agonist met-enkephalin into hippocampus of kindled rats resulted in the increase in the severity of seizure reactions which were induced by picrotoxin and also in the increase in the number of animals with postictal explosiveness. The injection of dynorphin-A-1-13 (kappa-opiate agonist) into substantia nigra reticulata induced the locomotor depression which was like one in postictal period and resulted in the decrease of picrotoxin-induced seizures severity. It was concluded that mu-opiate system of hippocampus took part in the formation of generator of pathologically enhanced excitation in the structure during kindling and the development of seizure syndrome, providing also the postictal explosiveness. Kappa-opiate system of substantia nigra plays an important role in the activation of the antiepileptic system, limitation of seizures and the development of postictal depression.
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PMID:[The role of the opiate mechanisms of the hippocampus and substantia nigra in the behavioral and convulsive disorders in picrotoxin-induced kindling]. 167 96

Stimulation of the perforant path, a major input to the hippocampal formation, produced significant decreases in the hippocampal levels of methionine enkephalin, dynorphin A(1-8) and an increase in the hippocampal level of gamma-aminobutyric acid. In addition, it was also observed that both mu and delta opioid receptor antagonists reduce wet dog shakes elicited by perforant path stimulation. The antagonists did not affect the changes in hippocampal levels of methionine enkephalin, dynorphin A(1-8) or gamma-aminobutyric acid. The results demonstrate that endogenous opioids are involved in the wet dog shakes elicited by perforant path stimulation. Since electrographic seizure activity occurs in the hippocampus in conjunction with perforant path stimulation-induced wet dog shakes, these data provide further evidence that endogenous opioid peptides play an important role in regulation of limbic system epileptogenic phenomena.
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PMID:Opioid mu and delta receptor antagonists reduce wet dog shaking elicited by perforant path stimulation. 167 26

Recent experimental data indicate that endogenous brain ligands for the opioid receptors such as enkephalins, beta-endorphin (beta-End) and dynorphin (Dyn) may be involved in both generalized and partial seizures. The "tottering" (tg/tg) mouse provides an electrophysiological representation of generalized spontaneous human epilepsy. These mice exhibit behavioral absence seizures with accompanying spike-wave discharges. Methionine-enkephalin (M-Enk), beta-End and Dyn levels in various regions of brain were measured by radioimmunoassay (RIA) in 15-18-week-old tg/tg and control (+/+) mice to elucidate the relation between seizures and the opioid system. beta-End and Dyn levels were similar in tg/tg and +/+ mice. However, M-Enk levels were significantly increased in the striatum, cortex, pons and medulla of the tg/tg mice. Our data suggest that in the tottering mouse model of generalized epilepsy there is an alteration of enkephalinergic pathways and not of the endorphinergic or dynorphinergic pathways.
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PMID:Increased methionine-enkephalin levels in genetically epileptic (tg/tg) mice. 168 15

Seizure-induced plasticity, in the form of either changes in cellular morphology or changes in neurochemistry, could have a profound impact upon regional excitability in brain. There is now ample evidence that in genetically 'normal' animals, seizure activity stimulates alterations in neuronal gene expression which could lead to changes in levels of excitability and, hence, to changes in the susceptibility for further seizures. Here we describe the influence of limbic seizures upon the expression of nerve growth factor (NGF), 2 related neurotrophic factors, brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3), and several neuropeptides (enkephalin, dynorphin, and neuropeptide Y) in the rat forebrain. Using 35S-labeled riboprobes and in situ hybridization methods, the effects of recurrent limbic seizures and of individual hippocampal paroxysmal discharges have been evaluated. Recurrent seizures are found to increase levels of mRNAs for NGF and BDNF and to decrease levels of mRNA for NT3 within select hippocampal neurons. Temporally distinct increases in the expression of mRNAs for NGF and BDNF are also observed across broad fields of neocortex, paleocortex (entorhinal, piriform, and cingulate cortices), and the amygdala. As little as one 20-sec paroxysmal discharge is sufficient to stimulate large changes in neurotrophic factor mRNA content of hippocampal neurons. The time courses and cellular specificities of these alterations in neurotrophic factor expression are discussed and contrasted with seizure-induced changes in neuropeptide expression. Mechanisms by which seizure-induced increases in hippocampal neuropeptide and neurotrophic factor synthesis could lead to both short- and long-term changes in regional excitability, and thereby could contribute to susceptibility for further seizure activity, are considered.
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PMID:Seizures and the regulation of neurotrophic factor and neuropeptide gene expression in brain. 181 5

The effects of systemic kainic acid (KA) administration on hippocampal levels of prodynorphin and proenkephalin mRNA, as well as opioid peptides derived from these precursors, were evaluated. A single subcutaneous injection of KA induced a range of seizure states, from mild wet dog shakes to generalized motor seizures. Northern blot analysis of hippocampal mRNA revealed an increase in both prodynorphin and proenkephalin mRNA levels which corresponded to the intensity of the convulsions. Conversely, hippocampal levels of immunoreactive dynorphin A (1-8) and [Met]5-enkephalin were decreased as a function of seizure frequency and intensity. The time course of KA-induced alterations in prodynorphin and proenkephalin mRNA and peptide levels was also investigated. Hippocampal prodynorphin mRNA levels rose at a dramatic rate. At 3 h following KA administration, mRNA levels were maximally elevated approximately 13-fold. The levels decreased over a 48 h period, eventually reaching control values. In contrast, proenkephalin mRNA levels increased more slowly. At 24 h, a maximal 24-fold increase was observed. At 72 h after injection, proenkephalin mRNA levels were still slightly elevated. In the same experiment, immunoreactive enkephalin peptide levels, although somewhat decreased at 3-12 h, began to increase between 12 and 24 h after injection, and were still rising at 72 h. In marked contrast, immunoreactive dynorphin peptide levels ranged from 40% to 80% of control values at all times tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Systemic administration of kainic acid differentially regulates the levels of prodynorphin and proenkephalin mRNA and peptides in the rat hippocampus. 185 80

By means of RIA, the contents of Leu-enkephalin, Met-enkephalin, and Beta-endorphin in CSF of 32 epileptic patients and 24 controls were determined. It was found that the mean Leu-enkephalin content in CSF of the epileptic patient group was significantly higher than that of the control group (P less than 0.01), whereas the mean contents of Met-enkephalin and Beta-endorphin in CSF showed no significant change as compared with those of the control group. The increase of Leu-enkephalin was not related to such factors as type of seizure, age of onset, length of time after the last seizure, taking of antiepileptic drugs, and abnormality in cranial CT manifestation. This suggested that endogenous opioid peptides might take part in the neurochemical mechanism of human epilepsy, and leu-enkephalin could play an important role in the development of epileptic episodes.
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PMID:[Opioid peptides in cerebrospinal fluids of epileptic patients]. 190 3


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