UMLS:C0036572 - FACTA Search

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

Diazepam's impact on kainic acid seizure-induced local cerebral glucose utilization (LCGU) was assessed by a quantitative [14C]2-deoxyglucose method. Male rats were injected i.p. with either kainic acid (12 mg/kg) or its vehicle, 3 or 48 h before LCGU determination. Diazepam (3.2 mg/kg) or its vehicle were injected i.m. 15 min before, 1 and 2.5 h after kainic acid. Diazepam blocked kainic acid-induced overt convulsions, attenuated LCGU increases at 3 h and prevented 48 h LCGU decreases in piriform cortex and amygdala. LCGU in (% of vehicle): CA3 (438%), CA4 (537%) and CA1-ventral (340%) of hippocampus, interpeduncular nucleus (200%) and lateral lemniscus (213%) were still significantly above vehicle levels in the 3 h diazepam-kainic acid group. These results suggest that diazepam suppresses the spread of kainic acid-induced seizure activity from the proposed CA3 epileptogenic focus. In addition, diazepam reduces, but does not abolish, hypermetabolic activity at the foci itself.
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PMID:Attenuation of cerebral glucose use in kainic acid-treated rats by diazepam. 369 39

In the rat hippocampal formation, degeneration of CA4-derived afferent fibers provokes the growth of mossy fiber collaterals into the fascia dentata. These aberrant fibers subsequently form granule cell-granule cell synapses. The hippocampal slice preparation was employed to determine whether these recurrent connections are electrophysiologically functional. Hippocampal slices were prepared 12 to 21 days after the bilateral destruction of CA4 neurons with either intracerebroventricular or intravenous kainic acid (KA). In slices from control rats, antidromic stimulation of the mossy fibers elicited a single population spike in the granular layer of the fascia dentata. In contrast, when slices from some KA-treated rats were similarly tested, antidromic stimulation elicited multiple population spikes. This effect was not reproduced by blocking inhibitory transmission with bicuculline methiodide. Slices from other KA-treated rats fired a single population spike, but an antidromic conditioning volley increased the amplitude of a subsequent antidromic population spike by 5 to 15%. In slices from control rats, on the other hand, an antidromic conditioning volley always either decreased or failed to alter the amplitude of an antidromic test response. Superfusion with Ca2+-free medium containing 3.8 mM Mg2+ reversibly abolished all effects of KA administration. Abnormal responses to antidromic stimulation correlated with the loss of CA4 neurons and the growth of supragranular mossy fiber collaterals in the same animals. These results suggest that supragranular mossy fiber collateral sprouts form a functional recurrent excitatory circuit. These aberrant connections may further compromise hippocampal function already disrupted by neuronal degeneration, such as by facilitating seizure activity.
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PMID:Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid-treated rats. 398 Dec 41

Neuronal necrosis in the brain resulting from status epilepticus of 15 to 120 minutes duration in ventilated and well-oxygenated rats was assessed. Seizures were induced by inhalation of the convulsant gas flurothyl, and terminated by withdrawal of flurothyl and a single injection of thiopental. The animals were allowed to recover for one week, and neuronal damage was assessed by cell counts following subserial sectioning of the brain and microscopical examination of the sections. Infarction of the pars reticulata of the substantia nigra occurred in 5 of the 6 animals with seizure duration of 30 minutes, and in all animals with longer seizure durations. There also was a common affectation of the central parts of the globus pallidus. The pars compacta of the substantia nigra was never affected. After 45 to 120 minutes of seizures, moderate neuronal necrosis was observed in the neocortex (layers 3 and 4), and after 60 to 120 minutes was seen in amygdaloid and thalamic nuclei, as well as in CA4 and CA1 hippocampal pyramidal cells. Notably, CA3 neurons were not damaged nor were dentate granule cells affected. After 120 minutes of seizures, damage regularly affected the neocortex and the ventral-posterior nuclei of the thalamus. A conspicuous feature was the localization of neuronal necrosis at sites close to the ventricles.
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PMID:Status epilepticus in well-oxygenated rats causes neuronal necrosis. 405 57

Intrahippocampal infusion of nanogram amounts of the neurotoxin kainic acid were used to investigate possible relationships between the convulsive and the local neurodegenerative properties of the amino acid. Bilateral hippocampal depth electrodes and cortical leads were employed to provide simultaneous and continuous electroencephalographic records following kainate injection in unanesthetized freely-behaving rats. In every animal, morphological analysis was performed 3-5 days after administration of kainic acid and attempts were made to correlate neuronal destruction with electroencephalographic patterns. Doses as low as 500 pg kainate led to behavioral sequelae consisting of grooming, scratching and enhanced locomotor activity. In a roughly dose-dependent fashion (range 500 gp-250 ng), these behaviors increased in frequency and at the highest doses the rats also displayed wet-dog shakes, stereotype mouth movements and occasional facial myoclonus. Apart from these automatisms, generalized motor seizures were never seen. Following kainic acid, a spectrum of electroencephalographic changes could occur consisting of one or more of the following: high voltage fast activity, slow and fast high voltage spiking, paroxysmal bursts, spindle bursts or postictal depression periods. The combination of any two of these changes were defined as an ictal episode if they occurred in all four leads simultaneously. Upon morphological examination, only the highest dose used (250 ng) resulted reliably in the degeneration of CA3, CA4 and, partly, CA1 pyramidal cells on the injected side. While the duration of electroencephalographic changes at this dose was significantly higher than at any of the lower doses, the number of seizures or the total time spent in seizures was not different at 250 ng from that at 50 ng. At the latter dose, however, only marginal cell damage could be found. Our data indicate that very low doses of kainic acid directly applied to hippocampal CA3 neurons, can elicit bilateral changes in the electroencephalogram indicative of repetitive limbic seizures which are not necessarily accompanied by neuronal degeneration. At higher doses (250 ng), kainic acid treatment results in both seizure activity and nerve cell death but the two effects appear mechanistically unrelated. While there is no clear-cut dose-response relationship between neuronal damage and seizures, extended electroencephalographic changes of a 15-30 Hz fast activity or simple spiking phenomena may be instrumental for the degenerative process. This dissociation between convulsive and neurodegenerative properties of kainic acid, however, does not argue against a role of an endogenous substance related to kainic acid in the etiology of temporal lobe seizure disorders.
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PMID:Intrahippocampal kainic acid, seizures and local neuronal degeneration: relationships assessed in unanesthetized rats. 717 85

Electrolytic lesions of the lateral hypothalamus (LH) are known to produce severe and chronic behavioral and electrographic abnormalities. In order to assess the effects of damage to LH cells vs damage to fibers of passage in the LH, a comparison was made of the effects of electrolytic lesions and microinjections of the neurotoxin kainic acid (kainate) in the LH. Behavior and neocortical and hippocampal electroencephalographic (EEG) activity were studied before, immediately after, and for 25 days after the lesions were made. Electrolytic-lesioned rats were aphagic and adipsic, showed an absence of normal atropine-resistant EEG activity, and a release of atropine-sensitive EEG activity in the hippocampus and neocortex. Kainic acid-lesioned rats showed some similar behavioral impairments but the kainate lesions produced different EEG abnormalities, including chronic slow-wave and seizure activity in both the neocortex and hippocampus. Following extended recovery hippocampal EEG was normal despite extensive cellular loss in areas CA3 and CA4. Understanding of the differences in EEG between the electrolytic and kainate effects was compounded by widespread cellular damage in areas outside the hypothalamus in the rats with kainate lesions. Thus, the kainate-produced abnormalities precluded a simple analysis of the contribution that cell damage alone makes to LH lesion-induced behavioral and EEG changes.
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PMID:Effects of kainic acid lesions in the lateral hypothalamus on behavior and hippocampal and neocortical electroencephalographic (EEG) activity in the rat. 723 51

This study determined differences of fascia dentata (FD) peptide and inhibitory neuroanatomy between patients with epileptogenic hippocampal sclerosis (HS), those with extrahippocampal seizure pathologies, and autopsy comparisons. Surgically treated temporal lobe epilepsy patients were clinically classified into two pathogenic categories: (1) HS with focal mesial temporal neuroimaging and histories of initial precipitating injuries to the brain (n = 18) and (2) non-HS patients with extrahippocampal mass lesions or idiopathic seizures (i.e., without lesions or HS; mass lesion/idiopathic; n = 9). The hippocampal sections were studied for (1) granule cell, hilar, CA4, and CA3 neuron densities; (2) hilar densities and the percentage of neurons immunoreactive (IR) for neuropeptide Y (NPY), somatostatin (SS), and glutamate decarboxylase (GAD); (3) densities of GAD neurons in the lower granule cell and infragranular zone (basket-like cells); (4) the semiquantitative pattern of IR peptides/GAD FD molecular layer axon sprouting; (5) IR gray values (GV) of the FD molecular layers; and (6) the thickness of the supragranular molecular layer. Results showed the following. (1) Compared to autopsies, both HS and mass lesion/idiopathic patients showed less granule cell and CA3 neuron densities, but there were no statistical differences between the latter two pathogenic categories. (2) By contrast, compared to autopsies and mass lesion/idiopathic cases, HS patients showed less hilar and CA4 neuron densities, and there were no differences between autopsies and mass lesion/idiopathic. (3) Compared to autopsies, the NPY and SS hilar neuron densities in HS patients, but not mass lesion/idiopathic cases, were less. (4) Compared to autopsies, the hilar GAD neuron densities for HS and mass lesion/idiopathic patients were not less. (5) In HS patients the averaged percentages of hilar SS neurons were less than autopsies, and no other differences of IR hilar percentages were found. (6) The densities of GAD basket-like neurons and the thickness of the supragranular molecular layer were not different between any combination of pathogenic categories and autopsies. (7) By semiquantitative visual assessments, peptides/GAD axon sprouting into the FD was greater in HS compared to mass lesion/idiopathic or autopsies. (8) Compared to mass lesion/idiopathic cases, in HS NPY outer molecular layer GVs were lower, SS GVs were not different, and GAD inner molecular layer GVs were higher. (9) Analyses comparing the two pathogenic categories and neuron densities with peptides/GAD axon sprouting found six comparisons that correlated sprouting with hilar and CA4 neuron losses, and four comparisons showing greater sprouting in HS compared to mass lesion/idiopathic.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Reactive synaptogenesis and neuron densities for neuropeptide Y, somatostatin, and glutamate decarboxylase immunoreactivity in the epileptogenic human fascia dentata. 775 60

Area CA3 of the hippocampus is the most epileptogenic structure of the brain. Various studies have shown that kainate-induced experimental epilepsy in rats and human cases of epilepsy are associated with sprouting of the mossy fibers of the dentate granule neurons and selective loss of pyramidal neurons, notably in the CA3-CA4 areas of Ammon's horn. In experimental models of epilepsy, brief seizure activity initiates a cascade of molecular alterations that will contribute to changes in the expression of numerous genes, which can last several weeks. The products of some of these genes will contribute to the permanent state of enhanced synaptic efficiency, to the sprouting and formation of novel excitatory synapses, and possibly to neuronal cell loss. The expression of genes encoding transcription factors and numerous growth factors is rapidly altered following seizure episodes. Based on observations in vivo and in vitro in cultured hippocampal neurons, it is hypothesized that an interplay between transcription and growth factors, because of their pleiotropic effects on the regulation of effector genes, may be instrumental in coupling transient extracellular stimuli to irreversible cellular alterations.
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PMID:Molecular correlates between reactive and developmental plasticity in the rat hippocampus. 777 75

Quantified hippocampal mossy fiber synaptic reorganization and neuron losses were measured to determine the pathological features associated with epileptogenic fascia dentata. Twenty-five patients with temporal lobe epilepsy (TLE) were classified as having either mesial temporal sclerosis (MTS; 16 patients), with seizure genesis in the hippocampus, or temporal mass lesions (nine patients), with seizures that were probably extrahippocampal. Neo-Timm's histochemistry identified mossy fiber sprouting, and aberrant fascia dentata puncta densities were objectively measured by light microscopic analysis on an image-analysis computer. neuron densities determined cell losses and the two seizure groups were compared to control specimens obtained from autopsies. Results showed significantly greater fascia dentata mossy fiber puncta densities and neuron losses in TLE patients compared to autopsy specimens (p < 0.026). Furthermore, there were significant differences between the two seizure groups: 1) mossy fiber puncta densities in the inner molecular layer were significantly greater in MTS compared to lesions (p < 0.02), and 2) mossy fiber puncta densities were greater in the inner molecular layer than in the stratum granulosum in 14 of 16 MTS patients (88%) compared to four of nine patients with lesions (44%, p < 0.01). Neuron densities were significantly different comparing MTS, lesion and control groups for stratum granulosum (p = 0.0001) and Ammon's horn (p = 0.0001), with each group significantly different (p < 0.05) compared to another. All patients were either seizure-free or significantly improved 1 year or more after en bloc temporal lobectomy. There were no significant correlations between fascia dentata mossy fiber puncta densities and counts of hilar neurons, CA4 pyramids, granule cells, or years of seizures. This indicates that inner molecular layer mossy fiber puncta densities and neuron losses are greater in patients with MTS than in those with lesions, and mossy fiber sprouting probably contributes to the pathophysiology of hippocampal seizures. Furthermore, these data show that some patients with extrahippocampal lesions have mossy fiber sprouting similar to MTS patients, suggesting that hippocampi in lesion patients may be capable of epileptogenesis from synaptic reorganization.
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PMID:Quantified patterns of mossy fiber sprouting and neuron densities in hippocampal and lesional seizures. 781 48

Alterations of gamma aminobutyric acid (GABA)-mediated neurotransmission have been implicated in the pathogenesis of epilepsies. Here we examine the distribution of the GABAA receptor in the hippocampus of 78 surgical specimens from patients with chronic pharmacoresistant focal epilepsies. The receptor was localized immunohistochemically with the monoclonal antibody bd-24 which selectively recognizes the alpha 1 subunit of the GABAA receptor. The results were compared with the receptor distribution of 28 normal hippocampal specimens obtained at autopsy. In the great majority of the surgical specimens a loss of GABAA receptor immunoreactivity was present in CA1 (92.3%), CA4 (78.2%), the dentate granular cell layer (70.5%) and the molecular layer of the dentate gyrus (65.4%). The subiculum revealed a normal staining pattern in all but 4 cases. In no instance did we observe an increase of immunoreactivity in any region or cell population. The decrease of GABAA receptor immunoreactivity was closely related to neuronal loss in the respective specimen and to Ammon's horn sclerosis. There was no correlation between GABAA receptor loss and the patient's age at surgery, duration of seizures, age at onset of seizures and to the presence or absence of secondary generalized tonic clonic seizures. The data suggest that the observed loss of GABAA receptor immunoreactivity is a secondary phenomenon rather than an event that is relevant for the pathogenesis of epileptic seizures.
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PMID:Hippocampal loss of the GABAA receptor alpha 1 subunit in patients with chronic pharmacoresistant epilepsies. 783 24

This study determined differences in clinical-pathologic characteristics of intractable temporal lobe epilepsy (TLE) patients whose mechanism of cerebral injury and chronic seizures involved a prior history of cerebral trauma compared to those with non-traumatic initial injuries. TLE patients (n = 120) from a single epilepsy center were retrospectively and blindly catalogued into pathogenic groups (independent variables) based on if there was a significant Birth injury (n = 11) or Cerebral trauma (n = 26). These two 'trauma' categories were compared to TLE patients with non-seizure non-trauma histories (Non-Sz/Non-Trauma; n = 17), or a first Prolonged seizure (n = 66). The four groups were compared for differences in the time course of their clinical injuries and seizures, quantified hippocampal neuron counts, other temporal neocortical pathologies, and seizure outcomes (dependent variables). Between group statistically significant (at least P < 0.05) results showed: (1) In Birth injury, 33% had Ammon's Horn (AH) neuron loss under 50%, 54% had other temporal neocortical pathologies, they showed the most CA4 neuron loss, and the worse seizure outcomes. (2) Cerebral trauma were older when injured, 29% had AH loss under 50%, 50% showed other pathologies, and they had the best seizure outcomes. (3) Non-Sz/Non-Trauma showed the least AH and CA4 neuron losses, only 12% had other temporal pathologies, and they had seizure outcomes that were intermediate. (4) Prolonged seizure showed the youngest age of habitual TLE onsets, the greatest AH, CA1, and prosubiculum neuron loss, only 11% had other temporal pathologies, and their seizure outcomes were excellent. These results indicate that in intractable surgically treated TLE, a history of cerebral trauma or birth injury as the pathogenic mechanism of their seizures show different clinical-pathologic features and seizure outcomes compared to non-trauma patients. This supports the notion that in TLE there are different pathogenic mechanisms associated with different types of initial injuries and that patients will have different responses to surgical therapy.
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PMID:Traumatic compared to non-traumatic clinical-pathologic associations in temporal lobe epilepsy. 784 68

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