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

The aims of this study were to examine the relationships of hippocampal T2 (HCT2) relaxation time and magnetic resonance (MR)-based hippocampal volume (HCV) to neuronal (ND) and glial cell densities (GD) of hippocampal neuronal cell layers, and to obtain a better clinicopathological definition of hippocampal sclerosis (HS) and end folium sclerosis (EFS). Fifty-three hippocampi with HS, 6 with EFS, and 6 control hippocampi were studied. Pathologically, the HS group had a significantly higher logarithm (log) GD/ND than the controls in all hippocampal subregions, and than the EFS group in all subregions except the granule cell layer of the dentate gyrus (GCDG). The EFS group had a significantly higher log GD/ND than the control group only in the GCDG. Clinical correlations suggested that EFS may be the consequence of temporal lobe seizures and not an epileptogenic entity. Hippocampal atrophy in HS was associated with neuronal cell depletion and concomitant gliosis in the cornu Ammonis (CA) 1, CA2, CA3, and hilus. An increased HCT2 was associated with damage in the CA1 and also the hilus and has a different neuropathological basis than HCV loss. MR-based HCV measurement and HCT2 mapping, therefore, give complementary information in the presurgical evaluation of temporal lobe epilepsy and longitudinal studies.
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PMID:Quantitative neuropathology and quantitative magnetic resonance imaging of the hippocampus in temporal lobe epilepsy. 939 75

This study was designed to determine whether hippocampal neuronal AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and NMDA (N-methyl-D-aspartate) mRNA levels were differentially increased in temporal lobe epilepsy patients compared with those measured in control tissue from non-seizure autopsies. Hippocampi from hippocampal sclerosis patients (n = 28) and temporal mass lesion cases (n = 12) were compared with those from the autopsies (n = 4), and studied for AMPA GluR1-3 and NMDAR1-2 mRNAs using semi-quantitative in situ hybridization, along with fascia dentata and Ammon's horn neuron densities. Compared with the autopsies, and without correction for neuron counts, the mass lesion cases with neuron densities similar to autopsies showed: (i) significantly increased NMDAR2 hybridization densities for fascia dentata granule cells; (ii) increased AMPA GluR3 mRNA densities for Ammon's horn pyramids; and (iii) similar or numerically increased mRNAs for all other subunits and hippocampal subfields. Compared with the autopsies, hippocampal sclerosis cases with decreased neuron densities showed: (i) significantly decreased AMPA GluR1-2 and NMDAR1-2 hybridization densities for Ammon's horn pyramids and (ii) similar or numerically decreased mRNAs for all other subunits and subfields. However, correcting for changes in neuron densities showed that hippocampal sclerosis patients had increased AMPA and NMDA mRNA levels per neuron compared with autopsies, and in the CA2 resistant sector GluR2 mRNA levels were numerically greater than autopsies and mass lesion cases. Furthermore, relative to autopsies both sclerosis and mass lesion hippocampi showed that, in the stratum granulosum, the greatest mRNA increases were in AMPA GluR1 and NMDAR2 compared with the other mRNAs. In chronic temporal lobe seizure patients these results indicate that mass lesion and sclerosis cases show differential increases in hippocampal AMPA and NMDA mRNA levels per neuron compared with autopsies, especially for AMPA GluR1 and NMDAR2 in fascia dentata granule cells. These findings support the hypothesis that temporal lobe seizures are associated with increased ionotropic glutamate receptor mRNA levels and alterations in receptor subunit composition that probably contribute to neuronal hyperexcitability, synchronization and seizure generation.
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PMID:Human hippocampal AMPA and NMDA mRNA levels in temporal lobe epilepsy patients. 939 13

Receptor autoradiography with the Y2 receptor ligand 125I-peptide YY3-36 and in situ hybridization were applied to investigate changes in neuropeptide tyrosine-Y2 receptor expression after kainic acid-induced recurrent seizures in the rat hippocampus. In the strata oriens and radiatum of CA1 to CA3, which are densely innervated by Y2 receptor-bearing Schaffer collateral terminals, a transient 2-fold increase in Y2 receptor affinity was observed after 4-12 hr, with a later slow decline. No change was seen in Y2 mRNA expression in CA2/CA3 pyramidal cells, from which Schaffer collaterals originate. Conversely, in granule cells of the dentate gyrus, markedly elevated Y2 mRNA concentrations were observed (by 740% in the dorsal hippocampus) 24-48 hr after kainate injection. At the same time, a marked and lasting (up to 6 months) increase in the number of Y2 receptor sites (by 800%) was seen in the dentate hilus, which is innervated densely by mossy fibers. The early increase in Y2 receptor affinity in Schaffer collaterals was accompanied by a 60% decrease in the EC50 of peptide YY3-36 in inhibiting K(+)-stimulated glutamate release in hippocampal slices from kainic acid-treated rats. Our data indicate transient up-regulation of presynaptic Y2 receptors in Schaffer collaterals by a change in affinity and a permanent de novo synthesis of presynaptic Y2 receptors in granule cells/mossy fibers. These changes may cause augmented presynaptic inhibition of glutamate release from different hippocampal sites and, in conjunction with increased concentrations of neuropeptide tyrosine in mossy fibers, may represent an endogenous reactive anticonvulsant mechanism.
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PMID:Up-regulation of neuropeptide Y-Y2 receptors in an animal model of temporal lobe epilepsy. 944 27

Rat CNS adenosine A1 receptors were studied by quantitative autoradiography after the administration of convulsant 3-mercaptopropionic acid (MP) and an adenosine analogue cyclopentyladenosine (CPA), using 2-chloro-N6-[cyclopentyl-2,3,4,5-3H adenosine]-([3H]CCPA) as radioactive ligand. Specific binding was quantified in hippocampus, cerebellum, cerebral cortex, thalamic nuclei, superior colliculus and striatum, and the highest densities were found in CA1, CA2, and CA3 hippocampus subareas and the lowest levels in superior colliculus and striatum. MP administration (150 mg/kg, i.p.) produced significant increases in [3H]CCPA binding in CA1 subarea at seizure (15%) and postseizure (21%) and in CA2 at seizure (15%) but a tendency to decrease in dentate gyrus. There was an increase in cerebellum at seizure (18%) but no significant changes in the other studied regions. CPA injection (2 mg/kg, i.p.) enhanced [3H]CCPA binding in CA1 and CA2 areas (17-18%) but not in CA3 area of the hippocampus. When CPA was administered before MP, which delayed seizure onset, an increase in [3H]CCPA binding in CA1 hippocampus subarea (19%) and cerebellum (28%) was also observed. Results showed that the administration of convulsant MP and adenosine analogue CPA exerts differential effects on adenosine A1 receptors in CNS areas; hippocampus is the most affected area with all treatments, specially CA1 subarea, supporting an essential role in convulsant activity as well as in seizure prevention.
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PMID:CNS adenosine A1 receptors are altered after the administration of convulsant 3-mercaptopropionic acid and cyclopentyladenosine: an autoradiographic study. 947 12

Administration of endogenous corticosterone to intact animals induces calbindin-D28k protein in the hippocampal CA1-CA2 subfields. The fact that this effect on calbindin-D28k was shown to be specific for the hippocampus argues for a receptor-mediated effect on gene expression. In addition, chronic pretreatment with corticosterone aggravates ischemia-induced neuronal damage in the CA3-CA4 subfields. This effect is similar to that of preischemic hyperglycemia, which also induces postischemic seizures and aggravates brain damage, since corticosterone raises blood glucose level and enhances tissue lactic acidosis during ischemia. The energetically compromising qualities of corticosterone indicates that it is a key factor in hippocampal vulnerability. We assume that the increase of calbindin-D28k expression in the CA1-CA2 subfields in corticosterone-treated animals is an adaptive response to the exogenous stress. The lack of adaptive response in CA3-CA4 neurons endangers them by impairing the ability of these neurons to counteract the deleterious effects of calcium. This finding, supports: (1) the hypothesis that corticosterone treatment, when paired with an ischemic insult, causes a prolonged elevation of neuronal [Ca2+]i, in an energy dependent manner, probably through the reduction of calcium efflux and (2) that neurons which do contain calbindin-D28k are particularly predisposed to ischemic insults. The CA1-CA2 neurons express high amounts of calbindin-D28k under stress conditions because their activity may involve a high rate of calcium buffering.
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PMID:Synergy between chronic corticosterone treatment and cerebral ischemia in producing damage in noncalbindinergic neurons. 950 Sep 60

Pentylenetetrazol is a convulsive drug acting on gamma-aminobutyric acid-A (GABA[A]) gated-chloride receptors. In this study we used a subconvulsive dose (30 mg/kg) of pentylenetetrazol to induce a fully kindled state in rats. Glutamate receptors were evaluated using [3H]-[1(2-thienylcyclohexyl)]-piperidin (TCP) and [3H]kainate receptor autoradiography and [3H]muscimol autoradiography was used to study GABA(A) receptors. In fully kindled rats decreased N-methyl-D-aspartate receptor binding was found in parietal cortex, area CA2 of hippocampus and piriform cortex. Decreased kainate receptor binding was observed in all areas of the hippocampus, the medial amygdala and in the piriform cortex in the kindled rats. In contrast, GABA(A) receptor binding increased in the dentate gyrus. It is concluded that modulatory neuronal plasticity events are induced in fully pentylenetetrazol kindled rats, which appears to lead to decreased glutamatergic excitation and increased GABAergic inhibition in brain regions implicated in the development of seizure activity.
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PMID:Pentylenetetrazol kindling decreases N-methyl-D-aspartate and kainate but increases gamma-aminobutyric acid-A receptor binding in discrete rat brain areas. 954 72

Adequate, high and deficient dietary levels of zinc (Zn) were compared in seizure-susceptible EL mice with respect to convulsions and to nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-positive hippocampal neurons. Diaphorase positivity is associated with nitric oxide (NO) production. Convulsive seizures in the EL mice given the various diets did not differ over 1-4 weeks, but convulsions in EL mice given the Zn-deficient diet for 4 weeks were more effectively suppressed by injection of zonisamide (ZNS) (75 mg/kg intraperitoneally) than in mice receiving high- or adequate-Zn diet for the same period. Numbers of NADPH diaphorase-positive neurons in the CA1/CA2 region of the hippocampal formation were significantly higher in mice given the Zn-deficient diet for 4 weeks than in mice fed adequate Zn. Mice receiving the high-Zn diet for the same period had significantly fewer NADPH diaphorase-positive neurons in the subiculum than mice with adequate Zn. These results suggest that Zn deficiency inhibits convulsive seizures of EL mice, and that dietary Zn influences numbers of NO producing neurons in the hippocampal formation.
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PMID:Influence of dietary zinc on convulsive seizures and hippocampal NADPH diaphorase-positive neurons in seizure susceptible EL mouse. 957 68

The effects of intrahippocampal administration of a neuropeptide (TS-8F toxin) isolated from Tityus serrulatus scorpion venom have been determined on behavior, limbic seizures, and neuronal degeneration in rats. Behavioral observation showed orofacial automatism, wet dog shakes, and myoclonus. Concomitantly, the electroencephalographic record showed high-frequency and high-voltage spikes that evolved to seizure activity in the hippocampus and cortex. Seven days after TS-8F toxin microinjection, neuronal damage was observed in CA1 and CA2 pyramidal cells and in granular cells of the dentate gyrus. The results suggest that TS-8F toxin may be responsible, at least in part, by the epileptic effects observed with the crude venom. Thus, this toxin may be a useful tool in the study of some neurobiological process.
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PMID:Behavioral, electroencephalographic, and histopathologic effects of a neuropeptide isolated from Tityus serrulatus scorpion venom in rats. 961 Sep 17

We studied brain synapsin I and II mRNA levels using the amygdala kindling model of epilepsy. There were significant increases in the synapsin I mRNA level in the granule cell layer of the hippocampal bilateral dentate gyrus. One to 8 h after seizures, the level in the dentate gyrus ipsilateral to stimulation increased by 44.2-73.2%, compared with the control level. Of the time points investigated, the greatest increase in expression was observed 8 h after the kindled seizures. Furthermore, the synapsin I mRNA levels in the dentate gyrus contralateral to stimulation increased by 28.0% and 51.1%, 2 and 8 h, respectively, after the kindled seizures. Expression of this mRNA, however, did not change significantly in other areas examined, including CA1, CA2, CA3 and the polymorphic layer of the hippocampus and the perirhinal and temporal cortices. Synapsin II mRNA levels did not change significantly in any of the regions studied for up to 24 h after the seizures and synapsin II was presumed to have little involvement in kindling. We considered the locally elevated synapsin I mRNA levels in the bilateral dentate gyrus associated with kindling indicate that excitatory changes occur in the synaptic circuit in which the dentate granule cells participate. Synapsin I may be involved in the presynaptic molecular mechanisms underlying the neuronal plasticity in kindling.
Seizure 1998 Jun
PMID:Increases in mRNA levels for synapsin I but not synapsin II in the hippocampus of the rat kindling model of epilepsy. 970 Aug 37

The GABA(A) receptor is a ligand gated chloride channel consisting of five membrane spanning proteins for which 13 different genes have been identified in the mammalian brain. The present review summarizes recent work from our laboratory on the characterization of the immunocytochemical distribution of these GABA(A) receptor subunits in the rat brain and changes in immunoreactivity and mRNA expression after kainic acid-induced status epilepticus. A heterogeneous distribution of immunoreactive GABA(A) receptor subunits was observed. The most abundant ones were: alpha1, alpha2, alpha4, alpha5, beta2, beta3, gamma2, and delta. Alpha1, beta2, and gamma2 were about equally distributed in all subfields of the hippocampus; alpha4- and delta-subunits were preferentially found in the dentate molecular layer and in CA1; alpha2 was localized to the dentate molecular layer and CA3; alpha5 was found in the dendritic areas of CA1 to CA3; and beta1 was preferentially seen in CA2. Alpha1, beta2, gamma2 and delta were highly concentrated in interneurons. Kainic acid-induced seizures caused acute and chronic changes in the expression of mRNAs and immunoreactive proteins. Acute changes included decreases in alpha2, alpha5, beta1, beta3, gamma2 and delta mRNA levels (by about 25-50%), accompanied by increases (by about 50%) in alpha1, alpha4, and beta2 messages in granule cells (after 6-12 h). Chronic changes, characterized by losses in mRNA and immunoreactive proteins in CA1 and CA3, are undoubtedly due to seizure-related cell damage. However, compensatory expression of alpha2 and beta3 subunits, especially in CA3b/c, was observed. Furthermore, increases in mRNAs and immunoreactive proteins were seen for alpha1, alpha2 alpha4, beta1, beta2, beta3 and gamma2 in granule cells and in the molecular layer of the dentate gyrus at 7-30 days after kainic acid injection. The changes in the expression of GABA(A) receptor subunits, observed in practically all hippocampal subfields, may reflect altered GABA-ergic transmission during development of the epileptic syndrome. Increased expression of GABA(A) receptor subunits in the dendritic field of granule cells and CA3 suggest that GABA-ergic inhibition may be augmented at these levels. However, the lasting preservation of alpha1-, beta2-, and gamma2-subunits in interneurons could provide a basis for augmented inhibition of GABA-ergic interneurons, leading to net disinhibition.
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PMID:Expression of GABA(A) receptor subunits in the hippocampus of the rat after kainic acid-induced seizures. 976 15


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