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)

Autopsy study of a patient who died after an episode of prolonged unilateral status epilepticus revealed neuronal loss in the hippocampus on the epileptic side, with gliosis confined to the CA1 and CA3 fields. There was loss of the parvalbumin-immunoreactive gamma-aminobutyric acid (GABA)-ergic interneurons in the hippocampus on that side. There was also loss of the normal laminar pattern of substance P staining with increased substance P immunoreactivity in the supragranular plexus on that side. Met-enkephalin immunoreactivity was also increased in the outer molecular layer of the dentate gyrus on the epileptic side. Mossy fibers on the epileptic side stained more strongly with the Hicks' silver stain and with antibodies against glutamate and taurine, but less intensely with antibodies against calbindin. In the contralateral cerebellum, there was Purkinje cell loss, injury to the remaining Purkinje cells, and increased prominence of the Bergmann glia. Our observations show that prolonged unilateral seizure activity can be associated with specific histochemical changes in the human hippocampus.
 ...
PMID:Neuropathologic asymmetries in the brain of a patient with a unilateral status epilepticus. 171 86

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.
 ...
PMID:[Opioid peptides in cerebrospinal fluids of epileptic patients]. 190 3

Rats were submitted to a series of 10 daily electroconvulsive shocks (ECS). A first group of animals was killed 1 day after the last seizure and a second group 30 days later. Tyrosine hydroxylase (TH) activity was measured using an in vitro assay in the nucleus caudatus, anterior cortex, amygdala, substantia nigra, ventral tegmental area, and locus ceruleus. The mRNA corresponding to this enzyme (TH-mRNA) was evaluated using a cDNA probe at the cellular level in the ventral tegmental area, substantia nigra, and locus ceruleus. Met-enkephalin (MET)-immunoreactivity and the mRNA coding for the preproenkephalin (PPE-mRNA) were assayed in striatum and the central nucleus of the amygdala. The day after the last ECS an increase of TH activity was observed in the ventral tegmental area, locus ceruleus, and substantia nigra in parallel with a similar increase in the amygdala and striatum; in the anterior cortex TH activity remained unchanged. TH-mRNA was increased in the locus ceruleus, evidencing the presence in this structure of a genomic activation. The amounts of MET and PPE-mRNA were unaffected in the striatum but increased in the amygdala. Thirty days after the last ECS we observed a decrease of TH activity in the amygdala and of TH-mRNA amount in the ventral tegmental area. In the locus ceruleus TH-mRNA remained higher in treated animals than in controls whereas TH activity returned to control levels. These results demonstrate that a series of ECS induces an initial increase of the activity of mesoamygdaloid catecholaminergic neurons followed by a sustained decrease through alterations of TH gene expression which could mediate the clinical effect of the treatment.
 ...
PMID:Short- and long-term alterations of gene expression in limbic structures by repeated electroconvulsive-induced seizures. 196 90

As neuropeptides may play a role in the electrical kindling model of epileptogenesis, hippocampal somatostatin, Met-enkephalin and cholecystokinin were studied by immunocytochemistry in rats 24 h following full hippocampal kindling (three stage 5 seizures). As control animals we used sham-kindled rats, unoperated rats and rats subjected to a single electroshock-induced seizure. In addition, the distribution of septohippocampal, cholinergic fibers and hippocampal mossy fibers were studied by histochemistry. The important finding was that after kindling there was, as compared to unoperated control, (1) a marked increase of somatostatin immunoreactivity in cell bodies in the dentate hilus and their presumed projections area in the outer parts of the dentate molecular layer, and (2) a marked increase of Met-enkephalin immunoreactivity in hippocampal mossy fiber terminals. We found no evidence of aberrant sprouting of mossy fiber collaterals in the fascia dentata.
 ...
PMID:Increased somatostatin and enkephalin-like immunoreactivity in the rat hippocampus following hippocampal kindling. 197 72

The biochemical and pharmacological properties of an endogenous anticonvulsant substance(s) found in rat cerebrospinal fluid (CSF) following seizures are described. CSF taken from donor rats following a single maximal electroshock (MES) seizure caused significant elevations in seizure thresholds in naive recipient rats when intracerebroventricularly injected 15 min prior to exposure to the volatile convulsant flurothyl. Anticonvulsant activity was antagonized by pre-injection in recipients of high doses of naloxone or the selective delta-opioid receptor antagonist ICI 174,864. The anticonvulsant activity was also lost when the CSF was exposed to heat (90 degrees C) or immobilized trypsin. Although unaffected by the peptidase inhibitors thiorphan and bestatin, the anticonvulsant activity was significantly potentiated by a combination of aprotinin and bacitracin. Ultrafiltration of CSF revealed that the anticonvulsant activity passed through membranes with a 10,000 molecular weight cut-off, but was retained by membranes with a 5000 molecular weight cut-off. CSF removed from rats following MES had significantly increased concentrations of beta-endorphin-like, but not dynorphin A, Leu- or Met-enkephalin-like immunoreactivities relative to CSF from sham-treated rats. However, significant increases in Met-enkephalin-like immunoreactivity were measured following exposure of the CSF to the proteolytic enzymes trypsin and carboxypeptidase B, suggesting the seizure-induced presence of a higher molecular weight form of Met-enkephalin not recognized immunologically prior to enzyme exposure. These data reconfirm the anticonvulsant actions of postseizure CSF, and indicate that these effects require mediation through delta-opioid receptors in the recipient rat. These data additionally argue against these effects being mediated by Met-enkephalin, Leu-enkephalin or dynorphin A in the CSF, and suggest instead that anticonvulsant effects are attributable to a heat- and trypsin-sensitive opioid peptide(s) with a molecular weight approximately in the range of 5000-10,000 Da.
 ...
PMID:Characterization of opioid peptide-like anticonvulsant activity in rat cerebrospinal fluid. 245 10

The role played by Met-enkephalin (ME) in epileptic seizures was investigated, using 57 ME kindled rats and 10 saline injected control rats. Repeated microinjection of 10 micrograms ME into the right amygdala (AM) of male Wistar rats led to development of generalized convulsions. One week after the completion of ME kindling, 1 or 2 electrical stimulations (200-400 microA, 60 Hz, 1 sec) of the right AM of ME kindled rats resulted in generalized convulsions in 5 rats. The duration of after-discharge (AD) in the first generalized convulsion induced by electrical AM stimulation in the ME kindled rats was significantly longer than that in the first generalized convulsion induced by electrical stimulation in the saline treated control rats (P less than 0.05). One week after the completion of ME kindling, naloxone (10 or 20 mg/kg, i.p.) given 10 min before the infusion of ME into the other 3 ME kindled rats attenuated both convulsive behavior and electrographical seizures. With the progress of convulsive behavior, the frequency of wet-dog shakes (WDS) tended to decrease and was significantly lower after ME injection in the first stage 5 seizures than after the first ME injection (P less than 0.01). These results strongly suggest that ME has a potent epileptogenic effect on the rat brain which is caused by the opioid receptors. There are some differences between chemical kindling with ME and electrical kindling as indicated by the development of the AD duration and the WDS frequency.
 ...
PMID:Chemical kindling with Met-enkephalin and transfer between chemical and electrical kindling. 254 58

Microinfusion of morphine sulfate (50 nmol), [d-Ala2]-Met-enkephalin (35 nmol) or dynorphin A 1-13 (1 nmol) bilaterally into the substantia nigra significantly attenuated seizures induced by maximal electroshock in rats. This action was accompanied by stereotyped behavioral hyperactivity. These anticonvulsant and behavioral effects were antagonized by systemic naloxone administration; neither effect was observed after intranigral microinjection of dynorphin A 1-17 amide (1 nmol). These results are consistent with a mu opiate receptor-mediated inhibition of substantia nigra efferent neurons, and with the proposal that bilateral inhibition of nigral efferents attenuates seizure propagation. However, intranigral morphine failed to alter the severity of i.v. bicuculline seizures, indicating that opiate-mediated inhibition in substantia nigra is distinct from that produced by gamma-aminobutyric acid.
 ...
PMID:Infusion of opiates into substantia nigra protects against maximal electroshock seizures in rats. 298 11

The relationship between cerebral GABA content and susceptibility to seizures is addressed from the point of view of specific brain loci at which GABA synapses may control convulsive activity. The substantia nigra (SN) has been identified as a critical site at which GABA-agonist drugs act to reduce susceptibility to a number of types of experimentally induced generalized seizures. Moreover, the ability of GABA-elevating agents to protect against seizures in the maximal electroshock model is directly correlated with increases in GABA specifically in the nerve-terminal compartment of SN. Studies with 2-deoxyglucose indicate that a marked increase in metabolic activity in SN is a common feature of several types of generalized seizures; it is possible that some of this increased activity is associated with GABAergic nerve terminals that become activated in an attempt to suppress seizure spread. Because GABA has been shown to inhibit nigral efferents, it is likely that GABA terminals inhibit nigral projections that are permissive or facilitative to seizure propagation. In support of this, bilateral destruction of SN attenuated clonic and tonic chemoconvulsant and electroshock seizures. Other treatments capable of reducing nigral output, namely opiate agonists (morphine and D-Ala-Met-enkephalin), and substance P antagonist analogs, were also found to have anticonvulsant effects when applied bilaterally into SN. Thus, the seizure-facilitating nigral efferents may be subject to inhibition by both GABA and opiates and may normally be driven by substance P. Of the various outputs from SN, the GABAergic projections to thalamus, reticular formation and/or superior colliculus are most likely responsible for influencing seizure propagation. Experimental evidence does not indicate a significant role of pars compacta nigrostriatal dopamine neurons for controlling the various types of seizures subject to nigral influence. We propose that the inhibition of the GABAergic outputs from SN pars reticulata can suppress the progression of seizure discharge through circuits involving the target areas of these outputs. Because chemical or electrical stimulation of SN does not initiate convulsions, it appears that seizure activity generated elsewhere in the brain may be amplified or sustained by activity in these nigral outputs.
 ...
PMID:Role of the substantia nigra in GABA-mediated anticonvulsant actions. 301 Jun 76

Repeated spaced injection of small amounts of beta-endorphin or Met-enkephalin into the hippocampus or posterior amygdala of the rat led to the development of kindled generalized convulsions. Similar injection of morphine into the hippocampus or anterior amygdala resulted in epileptiform spiking followed by tolerance. The epileptiform spiking and convulsive behavior varied in a dose-related manner. Naloxone blocked or greatly attenuated the electrographic seizure and convulsive behavior. Prior kindling with beta-endorphin or Met-enkephalin significantly facilitated electrical kindling of the amygdala. Handling or conspecific threat potentiated the epileptiform spiking and convulsive behavior in some cases. The results indicate that the epileptogenic response to intracerebrally applied opioid peptides is site-specific within the rat brain, and they support the idea that endogenous opioid mechanisms may play a role in convulsive seizures. They also suggest a possible opiate-based mechanism for the stress-induced exacerbation of seizures.
 ...
PMID:Epileptiform effects of met-enkephalin, beta-endorphin and morphine: kindling of generalized seizures and potentiation of epileptiform effects by handling. 316 84

In this work we analyzed the immunoreactive-methionine-enkephalin (IR-Met-enkephalin) levels in several brain regions of rats sacrificed during the tonic extension, induced by acute treatment with pentylenetetrazol (PTZ). The results show an increased of IR-Met-enkephalin content in striatum but not in amygdala, hypothalamus, septum, hippocampus and cortex. To characterize whether this elevation of enkephalin levels in striatum corresponded to the releasable pool, we studied the in vitro efflux of this peptide in striatal slices of rats sacrificed during the seizures, in acute PTZ and in PTZ-kindled rats (kindling group I). In addition, PTZ-kindled rats were analyzed 24 h after the last stimulus (kindling group II). The striatal slices of acute group and kindling group I displayed a significant increase in the evoked release of IR-Met-enkephalin. However, no significant changes occurred from striatal slices of kindling group II animals. In vitro superfusion of GABA (100 microM) produced a approximately equal to 63% decrease in IR-Met-enkephalin released from striatal slices in both saline and acute PTZ-treated rats. Several studies suggest that opioid peptides may be released in the ictal phase of seizure in order to mediate some transient postictal behavior. Our results suggest that of several brain regions tested, only the striatal IR-Met-enkephalin may be released during the ictus to mediate postictal behavior in the acute PTZ treated and in PTZ-kindled rats. This effect may be regulated by the GABA system.
 ...
PMID:Pentylenetetrazol-induced seizures produce an increased release of IR-Met-enkephalin from rat striatum in vitro. 407 66


1 2 3 Next >>