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

In rabbits epileptiform seizures were induced by systemic application of methoxypyridoxine, an antimetabolite of vitamin B6. The regional distribution of GABA was measured in 11 brain structures, before the onset of the seizure and during the generalized convulsions. In brain regions with a high GABA level the GABA content drops already preictally, in contrast to the GABA poor structures where no preictal decrease takes place. From this it is concluded that there exist two GABA pools, a functional one containing the GABA for chemical transmission, which is exhausted already preictally giving rise to the seizure discharges, and a metabolic one, which is utilized as an additional energy-source during the convulsions. Due to the decrease of the hippocampal GABA the endings of the dentate gyrus granule cells, the giant boutons contacting the apical dendrites of the pyramidal cells of CA3 and CA4, can discharge unrestrained. An ultrastructural correlate of the increased excitation is demonstrated. The dense-core vesicles of the giant boutons fuse in an omega-shaped form with the presynaptic membrane of the spines. This fusion-phenomenon is observed in ultrathin sections as well as in freeze-fractured replicas of this region.
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PMID:Antivitamin B6 induced ultrastructural changes in the hippocampus of the convulsant rabbit and its biochemical correlates. 99 35

To examine the neurotoxic effects of domoic acid, an amnesic shellfish toxin, electroencephalographic and behavioural experiments were conducted on 38 rats. Injection of domoic acid (0.5-1.0 mg/kg intravenously, or 0.04-0.08 microgram intraventricularly) caused seizure discharges in the hippocampus, tonic-clonic convulsions, and death within a few days. Convulsions and ensuing death were prevented by diazepam. Animals pretreated with diazepam (5 mg/kg, ip) tolerated intraventricular dose of domoic acid 0.4 microgram, but showed a loss of pyramidal neurons mainly in the CA3, CA4, and a part of CA1 areas of the dorsal hippocampus. Learning of a radial maze task was severely impaired in naive rats after intraventricular injection of domoic acid (and diazepam, ip). In the animals previously trained on the maze task, domoic acid interfered with relearning of the same task. These effects appear similar to those of kainic acid and are analogous to the symptoms observed in humans who ingested mussels tainted with domoic acid.
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PMID:Neural and behavioural effects of domoic acid, an amnesic shellfish toxin, in the rat. 128 34

alpha-Dendrotoxin (Dtx), a snake polypeptide, increases neuronal excitability by blocking certain fast-activating, voltage-dependent K+ channels. Thus, the behavioural, electrocortical (ECoG) and neuropathological effects of Dtx, injected into rat brain areas, were studied. A unilateral injection of 35 pmol of Dtx into the CA1 hippocampal area or the dendate gyrus (DG; upper blade) immediately produced motor and ECoG seizures, followed at 24 h by multi-focal brain damage and significant neuronal loss. Whilst brain damage was seen bilaterally, significant neuronal loss occurred only in regions (CA1, CA3, CA4 and DG) ipsilateral to the site of injection. A lower dose (3.5 pmol) of toxin elicited motor and ECoG seizures but failed to produce brain damage. Seizures were observed 50 min after injecting Dtx (35 pmol) into the amygdala, though significant neuronal loss was not evident. 4-Aminopyridine (100 nmol), given into the CA1 area elicited a similar motor and ECoG pattern to that of Dtx except no brain damage could be seen at 24 h. Systemic pretreatment with antagonists of N-methyl-D-aspartate receptors (MK-801 or CGP 37849) did not protect against the effects typically evoked by injecting Dtx into the CA1 area.
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PMID:Production of seizures and brain damage in rats by alpha-dendrotoxin, a selective K+ channel blocker. 135 2

The relation between interhippocampal seizure propagation time (IHSPT) and anatomic alterations in the human epileptic hippocampus may provide insight into the pathophysiology of temporal lobe epilepsy (TLE). Using depth electrode recordings, we measured the time required for spontaneous seizures with onset in one hippocampus to become manifest in the contralateral hippocampus in 50 patients who underwent resection of the temporal lobe of seizure origin. Cell densities in individual hippocampal subfields were determined and correlated with mean IHSPT for each patient. Mean IHSPT was significantly and inversely correlated with cell counts in CA4 only (r = -0.38, p less than 0.01, Pearson's product correlation; r = -0.52, p less than 0.001, Spearman's rank order correlation). In 5 patients with bilateral independent hippocampal seizure onset who had temporal lobectomy and a diagnosis of mesial temporal sclerosis, mean IHSPT was consistently longer from the sclerotic temporal lobe than to it. These observations suggest that anatomic changes associated with chronic epilepsy alter propagation patterns. Because CA4 is believed to modulate the output of dentate granule cells and also has commissural connections to the contralateral homotopic area, the association of decreased CA4 cells with prolongation of IHSPT suggests that the observed anatomic alterations may actively (through increased inhibition) or passively (through decreased recruitment) interfere with various routes of seizure propagation.
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PMID:Anatomic correlates of interhippocampal seizure propagation time. 139 29

The authors examined hippocampal tissue removed during surgical procedures in 17 patients with intractable epilepsy who were found by preoperative magnetic resonance imaging or computerized tomography to have intra-axial masses in the temporal lobe. Neuronal densities in the cornu ammonis (CA) fields of the hippocampus and in the dentate granule cell layer were measured in hematoxylin and eosin-stained sections and were found to be lower compared to a group of 18 autopsy controls. The neuronal densities in all hippocampal fields except CA2 were related to the patient's age at seizure onset. Patients with an earlier onset of seizures had lower neuronal densities. With the exception of CA4, neuronal densities were not significantly related to the duration of the seizure disorder. Cell counts in all fields except CA2 were also related to the location of the lesion in the temporal lobe. Patients with mesial temporal lesions had lower neuronal counts. These results suggest increased vulnerability of hippocampal cytoarchitecture to proximal lesions with early ictal manifestation.
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PMID:Hippocampal pathology in patients with intractable seizures and temporal lobe masses. 156 34

A single systemic administration of acromelic acid, a novel kainate analogue (kainoid), induces a series of characteristic behavioral changes in association with selective damage of interneurons in the caudal spinal cord in adult rats. When an effective dose of acromelic acid (5 mg/kg) was systemically administered, forced extension of hindlimbs with or without cramps appeared in all rats. In the course of the intensified hindlimb extension, 10 of 16 rats suffered from generalized convulsive seizures during which 6 rats died without apparent neuropathological change. Of 4 surviving rats that experienced seizures, two developed long-lasting spastic paraparesis which remained unchanged for at least 3 months, whereas the other two were normal in behavior on the days following the administration. In lower doses (less than 4 mg/kg), the rats transiently displayed forced extension of hindlimbs, and in a higher dose (5.5 mg/kg), all rats died during an attack of severe generalized convulsion. Neuropathological changes were observed only in the rats with persistent paraparesis, in which neuron damage was identified selectively in small interneurons in the lumbosacral cord. The morphological change of the degenerated spinal interneurons resembles that of degenerated hippocampal CA1 pyramidal cells seen after systemic administration of kainate. Large motoneurons, spinal roots, and white matter of the spinal cord were well preserved. Unlike the case of systemic administration of kainate, other structures in the central and peripheral nervous system and muscles were morphologically intact except the hippocampal CA4 and the stratum moleculare-lacnosum in which there were reactive astrocytes. The regional difference between kainate-induced and acromelate-induced neuron damage suggests that systemically administered acromelic acid, a kainoid, induces selective neuron damage through activating a particular kainate receptor subtype. The clinicopathological feature of the paraparetic rats resembles closely that of stiffman syndrome, a progressive human neurological disorder with selective loss of interneurons in the spinal cord.
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PMID:Acromelic acid, a novel kainate analogue, induces long-lasting paraparesis with selective degeneration of interneurons in the rat spinal cord. 157 22

In situ hybridization techniques were used to analyse the spatiotemporal pattern of brain-derived neurotrophic factor messenger RNA elevation associated with kainic acid-induced seizure activity in the rat. Pronounced increases in hippocampal brain-derived neurotrophic factor messenger RNA levels were observed as early as 30 min following the onset of behavioral seizures. The greatest increase (10-fold) occurred in the dentate granule cell layer, while pyramidal layers CA1, CA3, and CA4 exhibited increases of two- to six-fold. Peak elevation of brain-derived neurotrophic factor messenger RNA in CA1 hippocampal region was evident at 4 h in CA3, and in the dentate granule layer at 30 min postseizure. Elevations persisted in the dentate and hilar regions to four days, while the increases in CA1 and CA3 returned to control levels by 16 h following seizure. Significant increases in brain-derived neurotrophic factor messenger RNA were also observed in the superficial layers of cortex (II and III) and in the piriform cortex which reached peak elevations by 8 h. No detectable changes were observed in the dorsomedial thalamus. Although histologically defined pyramidal and granule cell layers displayed relatively uniform increases in brain-derived neurotrophic factor messenger RNA in response to kainate, a closer examination of the labeling patterns using emulsion autoradiography revealed discrete areas of high grain densities overlapping uniform, moderate hybridization densities in the dentate granule cell layer and CA3, suggesting that the capacity to upregulate brain-derived neurotrophic factor messenger RNA in these regions may differ among individual neurons. In conclusion, our studies revealed that brain-derived neurotrophic factor messenger RNA induction in response to systemic kainate administration differs in hippocampal and cortical areas, in magnitude, time of onset and duration. The observed temperospatial pattern does not correspond in a simple way to increases in metabolic or electrical activity associated with seizures or neuronal vulnerability coincident with the seizures.
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PMID:Regionally specific and rapid increases in brain-derived neurotrophic factor messenger RNA in the adult rat brain following seizures induced by systemic administration of kainic acid. 164 Nov 25

Temporal lobe epilepsy is a common form of epilepsy in human adults and is associated with a unique pattern of damage in the hippocampus. The damage includes cell loss of the CA3 and CA4 areas and synaptic growth (sprouting) of mossy fibers in the supragranular layer of the dentate gyrus. Experimental evidence indicates that in adult rats the excitatory amino acid, kainic acid, induces a similar pattern of changes in hippocampal circuitry associated with alterations in perforant path excitation and inhibition. It has been suggested that, in humans, this type of damage may be a result of seizures early in life. In this study we examined the effects of kainic acid-induced status epilepticus on synaptic reorganization and paired-pulse electrophysiology in developing rats and adults. Kainic acid induced more severe seizures in 15-day-old rat pups than in adults. In contrast to adult rats, these seizures did not produce CA3/CA4 neuronal loss, mossy fiber sprouting or changes in paired-pulse excitation or inhibition in the hippocampus of rat pups tested 2-4 weeks after status epilepticus. Our results provide evidence that the immature hippocampus may be more resistant to seizure-induced changes than the mature hippocampus.
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PMID:Resistance of the immature hippocampus to seizure-induced synaptic reorganization. 171 81

Aminooxyacetic acid (AOAA), a potent yet nonspecific transaminase inhibitor, is known to cause convulsions when administered at high doses to experimental animals. The present study was designed to explore the mechanism(s) underlying the epileptogenic properties of AOAA. To this end, the drug was injected into the hippocampus of unanesthetized rats. Injection of 1.8 to 450 nmol AOAA produced dose-dependent EEG abnormalities including, at the higher doses, limbic seizures. Coadministration of the selective NMDA receptor antagonist D-2-amino-7-phosphonoheptanoic acid (APH) at doses of 45 and 225 nmol caused an almost complete inhibition of seizures produced by 225 nmol AOAA. At 225 and 450 nmol, AOAA also caused selective neuronal damage, which was restricted to the CA1 region at the lower dose and also affected the CA3/CA4 area in two of six rats injected with the higher dose. Co-injection of 225 nmol APH completely protected the hippocampus from AOAA-induced damage. In separate experiments, microiontophoretic application of AOAA to CA1 pyramidal neurons failed to increase the firing rate of each of the 10 cells tested, thus indicating that the drug does not directly activate NMDA receptors. These experiments suggest that seizures and neurotoxicity produced by AOAA are mediated indirectly via NMDA receptor activation.
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PMID:Focal injection of aminooxyacetic acid produces seizures and lesions in rat hippocampus: evidence for mediation by NMDA receptors. 183 21

We evaluated the ability of preoperative radiologic imaging to detect hippocampal sclerosis in 31 patients who underwent surgery for intractable epilepsy. Hippocampal sclerosis is commonly associated with surgically treatable temporal lobe epilepsy. It is pathologically described as neuronal cell loss with associated gliosis in the hippocampus. While previous reports have correlated imaging results with clinical or qualitative histologic findings, this study used quantitative pathologic criteria (neuronal cell density) to diagnosis hippocampal sclerosis. We focused our study on the 11 patients with cryptogenic temporal lobe epilepsy. Of these, nine had hippocampal sclerosis by pathologic criteria. MR findings included unilateral hippocampal atrophy, an increased signal in the hippocampus on long TR scans, and atrophy in the adjacent white matter and temporal lobe. Hippocampal atrophy was most frequently seen in the red nucleus plane on coronal scans, corresponding to the body of the hippocampus. We also compared hippocampal size on MR with neuronal density in surgical specimens of the 11 patients with cryptogenic temporal lobe epilepsy. A statistically significant correlation was found between MR size and neuronal density in CA3 and CA4 of the cornu ammonis and the granular cell layer of the hippocampus. Since temporal lobectomy eliminated seizures in seven of nine patients with hippocampal sclerosis, preoperative diagnosis by MR has important therapeutic consequences.
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PMID:Imaging findings in hippocampal sclerosis: correlation with pathology. 195 Sep 25


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