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

Transient ischemia in normoglycemic animals leads to delayed neuronal damage which is confined to selectively vulnerable regions. In at least one of these, the CA1 sector of the hippocampus, cell death is preceded by neuronal hyperactivity, presumed to be caused by loss of inhibitory control. Hyperglycemic subjects develop postischemic seizures, and show enhanced damage. The ATP-sensitive K+ channel, which may be important in inhibitory control, is the target of antidiabetic sulfonylureas. We determined densities of sulfonylurea binding sites in rat brain after forebrain ischemia. Normoglycemic animals showed a decrease of glibenclamide receptor binding in the CA3 field, hilus and dentate gyrus of the hippocampus after 1 day of recovery. After 4 days of recovery, levels of sulfonylurea binding sites decreased mainly in the CA1 field and in the hilus, as well as in the substantia nigra. After 1 day of recovery, hyperglycemic animals did not show any significant variations of densities of sites compared to control animals. It is proposed that reduction of inhibitory control by ATP-sensitive K+ channels may be associated with delayed neuronal death.
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PMID:Brain ischemia alters the density of binding sites for glibenclamide, a specific blocker of ATP-sensitive K+ channels. 212 31

1. To study the effects of brief periods of hypoxia on cellular functions in the rat hippocampal slice, extracellular and intracellular recordings were made from pyramidal neurons, and interstitial potassium activity ([K+]o) was measured in the pyramidal cell layers. Slices were perfused in an interface chamber at 36-37 degrees C with medium containing 8.5 mM [K+]o. Hypoxia was induced by switching the overflow gas from O2-CO2 to N2-CO2. 2. Brief periods of hypoxia (5-60 s) produced electrographic seizures with typical tonic and clonic components in 53% of 293 slices that generated spontaneous interictal bursts. Hypoxia-induced seizures were usually initiated in and restricted to the Ca1 region; only 2.5% of these slices generated seizures in CA3. In contrast to the CA1 region, the CA3 region could undergo spreading depression during hypoxia. The probability of seizure generation in CA1 was increased with increasing duration of hypoxia and was greatly reduced by lowering the bath temperature a few degrees. 3. [K+]o gradually increased in the CA1 and CA3 cell layers during the 20 s leading up to an hypoxia-induced seizure. [K+]o rose to approximately 9.8 mM (from a base line of 8.5 mM) in CA1 just before a seizure and to 11.4 mM during the seizure. After hypoxia, [K+]o reached a higher level in CA1 than in CA3, regardless of whether 1 microM tetrodotoxin was present to eliminate differences in cell firing in the two regions. CA1 pyramidal cells and glia gradually depolarized by several millivolts during and after hypoxia; no initial hyperpolarizing phase was detected. 4. Burst input from CA3 was necessary for hypoxia-induced seizures. The frequency and intensity of spontaneous burst-firing in CA3 remained steady in the period leading up to a CA1 seizure episode. In contrast, the intensity of synaptically driven bursts in CA1 grew markedly just before seizure onset. N-methyl-D-aspartate (NMDA) receptors participated in the crescendo of increasingly synchronous activity in CA1, because the competitive NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acid (D-APV, 30 microM), stereoselectively reduced seizure intensity. 5. Hypoxia-induced seizures were followed by a depressant phase, which was manifested most prominently by a prolonged (up to several minutes) reduction in the frequency and intensity of burst-firing in the CA3 region, hyperpolarization of CA1 neurons, and undershoot of [K+]o. In normal (3.5 mM) [K+]o, synaptically driven population spikes in CA1 were only reduced in amplitude by hypoxia; hypoxia did not induce seizures in 3.5 mM [K+]o.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Different responses of CA1 and CA3 regions to hypoxia in rat hippocampal slice. 215 21

In temporal lobe epilepsy, excitatory amino acid receptors in the hippocampus and temporal lobe may contribute to both increased excitability and vulnerability to excitotoxic damage. We used receptor autoradiography to examine the density of N-methyl-D-aspartate (NMDA) and kainic acid (KA) receptors in the hippocampus and parahippocampal gyrus obtained from five patients who had undergone anterior temporal lobectomy for the treatment of intractable seizures and from six control individuals, in which the hippocampus was obtained postmortem. Within the hippocampal formation, loss of [3H]KA and NMDA-sensitive L-[3H]glutamate binding was apparent in the sclerotic regions CA3, hilus, and CA1. In the subiculum and molecular layer of the denate gyrus, binding densities were maintained or even increased in some of the epileptic patients. A two-fold increase in L-[3H]glutamate binding, along with an increase in [3H]KA binding, was observed in the parahippocampal gyrus obtained from the epileptic patients. The results suggest that the vulnerability of the hippocampus in temporal lobe epilepsy may result, at least in part, from the presence of aberrant excitatory circuits in the parahippocampal gyrus.
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PMID:Altered distribution of excitatory amino acid receptors in temporal lobe epilepsy. 216 74

The role of the ventral hippocampal dentate granule neurons in the mu opioid receptor agonist-induced motor seizures and wet dog shakes was examined in this study. [NMe-Phe3-D-Pro4]morphiceptin (9.4 nmol) was injected into the left ventral hippocampus of rats 14 days after unilateral or bilateral colchicine (5 nmol/site) lesions of ventral hippocampal dentate granule cells and the subsequent behavioral and neuropathological responses were observed. [NMe-Phe3-D-Pro4]morphiceptin injected into control animals produced convulsions and numerous wet dog shakes that lasted for less than 1 h. [NMe-Phe-D-Pro4]morphiceptin-induced wet dog shakes were significantly reduced in unilateral colchicine-pretreated rats, and completely inhibited in bilateral colchicine-pretreated animals. In contrast, generalized motor seizures evoked by [NMe-Phe3-D-Pro4]morphiceptin were potentiated and prolonged in colchicine-pretreated animals as status epilepticus (sustained clonus of forepaws and head for more than 1 h) was observed in both unilateral and bilateral colchicine-pretreated animals but not in control rats. No morphological damage of granule or pyramidal cells was found in the ventral hippocampus of control animals following [NMe-Phe3-D-Pro4]morphiceptin injection. Colchicine treatment by itself produced a selective lesion of dentate granule cells. In colchicine-pretreated animals, [NMe-Phe3-D-Pro4]morphiceptin induced widespread seizure-related damage of CA3/CA1 pyramidal cells. These results suggest that dentate granule cells in the ventral hippocampus are essential for the elaboration of wet dog shakes. However, these neurons may play an inhibitory role in the spread of seizure activity within the hippocampus or limbic structures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ventral hippocampal dentate granule cell lesions enhance motor seizures but reduce wet dog shakes induced by mu opioid receptor agonist. 216 33

The aim of the present study was to investigate whether the hippocampus exerts a modulatory effect on the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Kainic acid was stereotaxically injected into the CA1 pyramidal cell layer of the dorsal hippocampus, causing histological and behavioural changes typical of kainic acid toxicity. The CA3 pyramidal cells of the dorsal hippocampus were selectively lesioned. Rats treated with kainic acid were hyperactive, executed clockwise rotatory movements and displayed epileptic seizures. The acute excitatory effect of kainic acid on glutamatergic receptors in the hippocampus resulted in an elevation in plasma corticosterone levels, suggesting a stimulation of HPA axis activity. Direct or indirect stimulation of the CA1 pyramidal cells of the dorsal hippocampus appeared to have caused the increase in corticosterone secretion.
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PMID:The effect of intrahippocampal injection of kainic acid on corticosterone release in rats. 216 46

Recent evidence implicates the endogenous excitotoxin, glutamate (Glu), in several neurologic disorders, including seizure-related brain damage. Ketamine, phencyclidine, and MK-801, which are noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) subtype of Glu receptor (but do not antagonize kainic acid receptors) were tested in the present study for their effects on behavioral and/or electrographic seizures and seizure-related brain damage induced by kainic acid. Behavioral seizure activity was reduced by these agents, as was spread of electrographic seizures to neocortex, but seizures recorded from deep brain regions such as hippocampus, piriform cortex, and amygdala were not significantly diminished. All three agents prevented seizure-related brain damage in the amygdala, piriform cortex, thalamus, and CA1 region of the hippocampus but conferred little or no protection in the lateral septum and CA3 region of the hippocampus. The regional selectivity of the neuroprotective effect suggests that NMDA receptors may play a more dominant role in seizure-related brain damage in some brain regions than in others. The ability of NMDA antagonists to prevent seizure-related damage in several brain regions without suppressing seizure activity suggests that in these brain regions persistent seizure activity can be maintained by other transmitter systems, with or without NMDA receptor participation, but that seizure-related brain damage is critically dependent on NMDA receptor participation.
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PMID:Ketamine, phencyclidine, and MK-801 protect against kainic acid-induced seizure-related brain damage. 219 69

Recent studies have demonstrated that the regulation of neuropeptide expression in forebrain neurons is responsive to external influences including changes in physiological activity. This has been demonstrated most clearly in studies of hippocampus where the synthesis and resting levels of several neuropeptides, localized within well-characterized components of hippocampal circuitry, have been shown to be selectively influenced by seizure activity. In studies described here, we examined the influence of recurrent limbic seizures on the expression of enkephalin, dynorphin, cholecystokinin, and neuropeptide Y (NPY) in rat and mouse hippocampus using immunohistochemical, in situ hybridization and blot hybridization techniques. The data demonstrate that seizures differentially influence the expression of each peptide as a part of a broader cascade of changes in genomic expression within individual hippocampal neurons. In particular, seizures increase preproenkephalin mRNA and enkephalin peptide but decrease dynorphin peptide in the dentate gyrus granule cell/mossy fiber system. Seizure-induced decreases in the concentration of preprodynorphin mRNA in the granule cells have been reported by others. Immunoreactivity for CCK, which is codistributed with the opioid peptides in the mossy fiber system of mouse, is also dramatically reduced in the granule cell axons by seizure. Recurrent seizures induce two temporally distinct changes in NPY expression in hippocampus. First, there is an increase in hybridization to preproNPY mRNA within scattered, probable local circuit neurons in all subfields. This is followed by the seemingly novel appearance of preproNPY mRNA within the dentate gyrus granule cells and pyramidal cells of field CA1. Clues about mechanisms of neuropeptide regulation have come from observations of other, more rapid, transcriptional events induced by seizure. Most notably, our results and those of others demonstrate that seizures increase the expression of messenger RNAs from immediate-early genes (c-fos, c-jun, and NGFI-A) which encode proteins that may mediate neuropeptide gene regulation. In addition, mRNA for nerve growth factor is dramatically increased in the dentate gyrus granule cells by seizure; increased production of this trophic factor might mediate the more delayed changes in genomic expression and growth responses observed to occur in hippocampus and other forebrain areas following seizure activity.
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PMID:Seizures, neuropeptide regulation, and mRNA expression in the hippocampus. 220 4

Thirty-five patients with medically refractory epilepsy localized to the temporal lobe (18 left, 17 right) completed the verbal Selective Reminding Test before surgery. Verbal memory impairments existed before surgery regardless of the lateralization of the seizure focus, but patients with left temporal seizure foci were significantly more impaired. After surgical removal of the mesial temporal lobe structures, 2 blinded observers established volumetric cell densities for hippocampal subfields CA1, CA2, CA3, the hilar area, and the granule cell layer of the area dentata. Statistically significant correlations existed between presurgical memory impairment and cell counts (in CA3 and the hilar area, only) for patients with left temporal seizure foci. These findings support the hippocampal model of memory and complement prior research documenting the memory impairments present after surgical removal of the mesial temporal structures.
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PMID:Verbal memory impairment correlates with hippocampal pyramidal cell density. 223 24

Adult female, Fischer-344 rats were exposed to 275 mg/kg of tris(2-chloroethyl)phosphate (TRCP) by gavage. TRCP produced consistent signs of convulsive activity within 60-90 min after dosing and extensive loss of CAT hippocampal pyramidal cells when examined 7 days after dosing. At the light microscopic level, toxic effects of TRCP on pyramidal cells in the CA3 and CA4 regions and on granule cells in the dentate gyrus were less severe than those on the CA1 cells. The seizure-related and neurohistological effects of TRCP were significantly attenuated by pretreatment with atropine or chlordizepoxide, suggesting that the hippocampal damage was related to the seizures produced by TRCP. In a second experiment designed to assess the potential health risk associated with TRCP, exposed rats were mildly impaired in the acquisition of a reference memory task in a water maze. However, TRCP-exposed rats were consistently impaired in performing a repeated acquisition task in the water maze. These data underscore the potential health risk associated with exposure to TRCP and support the conclusion that the hippocampus is intimately involved in spatial memory in rats.
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PMID:Acute exposure to tris(2-chloroethyl)phosphate produces hippocampal neuronal loss and impairs learning in rats. 225 15

The behavioural effects of tetanus toxin, injected into the rostral hippocampus, have been studied in rats. A single dose (1000 mouse minimum lethal doses; n = 10) of the toxin produced tail rigidity, hunched back and sound- and touch-evoked stimuli, 48 hr after the injection in all rats treated and these culminated in generalized convulsions 5-7 days later. Seizures were also observed 4 days after the injection of 2000 MLDs (n = 10), whereas a dose of 500 MLDs (n = 10) was ineffective. Similarly, dose- and time-dependent lethal effects were observed. In comparison to the contralateral (untreated) hippocampus, tetanus toxin (1000 MLDs; n = 3) produced a statistically significantly reduction in the number of cells in the CA1 pyramidal cell layer of the injected side, 7 and 10 days after the injection. No changes were observed in other sectors (CA2 and CA3 areas) of the hippocampus. In conclusion, the present experiments have shown that the focal injection of tetanus toxin into the hippocampus produced dose- and time-dependent behavioural stimulation and lethal effects in rats.
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PMID:Behavioural and neuropathological effects produced by tetanus toxin injected into the hippocampus of rats. 227 11


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