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

Kindling is a form of experimental epileptogenesis in which periodic electrical stimulation of a brain pathway induces a permanently hyperexcitable state. Previous studies suggested that kindling might be explained, at least in part, by an increased sensitivity of brain neurons to NMDA receptor agonists. This possibility was investigated with the use of grease-gap preparations for assaying the depolarizing responses of CA3 and CA1 hippocampal pyramidal cells to amino acid excitants. When studied 1-2 months after the last evoked seizure, CA3 pyramidal cells from kindled rats were five- to sixfold more sensitive to NMDA than CA3 pyramidal cells from controls. A similar, though smaller, effect of stimulation was observed 1 d after the last evoked seizure. The greater potency of NMDA in kindled rats can probably be explained by enhanced expression of NMDA receptors in the presence of a receptor reserve. The stimulation protocol did not alter the ability of Mg2+ to reduce NMDA potency. It also affected neither the response of CA3 pyramidal cells to AMPA [(RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate] nor the response of CA1 pyramidal cells to NMDA or AMPA. In area CA3, the potency of NMDA, but not of AMPA, declined 2.5-4-fold over the 1-2 month experimental period, apparently as a result of increasing age. This age-related loss of sensitivity to NMDA was completely prevented by kindling. These findings suggest that kindling prevents a loss of NMDA receptor function in CA3 pyramidal cells that normally occurs during early adulthood. Such a change could contribute to maintenance of the kindled state.
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PMID:Kindling enhances sensitivity of CA3 hippocampal pyramidal cells to NMDA. 137 64

Rats were given a single gavage of trimethyltin chloride (TMT) providing a dose of 0, 4.3, or 6.7 mg/kg of alkyltin. Gross changes in brain structures were quantified and analyzed statistically. Behavioral and functional measures were taken to verify efficacy of TMT dose. The high dose produced transient weight loss and seizures. In the fourth week after gavage, the high dose produced hyperactivity in the residential maze and activity wheel. High and low TMT doses decreased auditory startle responsiveness. Estrus cycle was normal in all groups. Brains were sectioned and stained with the Timm stain which delimited subregions of hippocampus and connected structures and also revealed mossy fibers. Linear and areal measures were made at three positions along the septotemporal axis of Ammon's horn. The low dose produced reductions in size in a few isolated subareas of the brain. The high dose produced, at the three planes studied, extensive (15-40%) loss of tissue in Ammon's horn and structures to which Ammon's horn is interconnected--subiculum, entorhinal cortex, dentate gyrus, hilus, CA3, and CA1 region. Neocortex and caudate-putamen were unaffected. These findings suggest that a single TMT gavage may disrupt brain structures important to linking neocortex with subcortex via structures in the hippocampal region.
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PMID:A morphometric analysis of trimethyltin-induced change in rat brain using the Timm technique. 137 83

Spontaneous seizures recorded from mesial temporal depth electrodes in the human are commonly manifested by one of two onset patterns: a high frequency discharge or a periodic spike discharge morphologically similar but clearly distinguished from ongoing interictal activity. We categorized medial temporal lobe seizure onset for the presence of periodic ictal spikes at a frequency of less than 2 Hz lasting for more than 5 sec to investigate the relationship of this ictal pattern to anatomical changes in the resected temporal lobe tissue. Fifty-one patients had hippocampal depth electrode recordings of spontaneous seizures, subsequent hippocampal resection, and quantitative cell counts of hippocampal subfields. Thirty-two of these patients had ictal spikes lasting at least 5 sec in more than 50% of their seizures. The presence of ictal spikes was significantly correlated with decreased cells in CA1 only (P = 0.015). The correlation of a common ictal pattern with focal cell loss in the hippocampus suggests that electrophysiological manifestations of seizures provide a clue to the underlying pathological substrate. Ictal spikes may be a cause or result of the cell loss. These observations should be correlated with independent investigations in humans and animal models that reflect the CA1 cell loss associated with temporal lobe epilepsy.
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PMID:Ictal spikes: a marker of specific hippocampal cell loss. 137 75

A few mouse minimum lethal doses (MLD) of tetanus toxin injected into rat hippocampus triggers prolonged changes in neuronal function. Spontaneously recurring epileptic discharges arise in both the injected and the contralateral, uninjected hippocampus. The seizures remit after about 6 weeks, to be succeeded by a permanent depression of hippocampal neuronal responses. There is no evidence of any loss of pyramidal cells at this low dose of toxin. Here we studied presumptive inhibitory, GABAergic neurons, using in situ hybridization (ISH) with a probe directed against the mRNA encoding glutamic acid decarboxylase (GAD), at each of 1, 2, 4 and 8 weeks after injection of tetanus toxin. Epileptic activity was recorded from hippocampal slices prepared from both injected and contralateral hippocampi of rats at each time point, unexpectedly persisting until 8 weeks. There were no significant differences in the numbers of neurons containing GAD mRNA between toxin- and vehicle-injected and control rats in any hippocampal subfield, at any survival time, except for an apparently transient loss of hilar signal in vehicle-injected rats at 1 and 2 weeks which we attribute to a significant, transient loss of neuronal GAD mRNA to below the threshold for detection by ISH using this probe. In contrast there was a marked increase in GAD mRNA in the toxin-injected group, which reached a peak at 4 weeks, and returned to control levels by 8 weeks. The changes were bilateral and were most marked in the hilus of the dentate area, but were also significant in CA3 and CA1. Upregulation of GAD mRNA was preceded by an increase in the levels of the mRNA for the alpha subunit of the GTP binding protein, Gs (Gs alpha), at 2 weeks which affected the GABAergic neurons selectively, and not the pyramidal or granule cells. These marked changes in GAD mRNA may contribute to putative adaptive responses within GABAergic neurons, which would help contain epileptic activity in these chronic foci. The changes in GAD expression may be due to mechanisms acting through an increase in mRNA encoding Gs alpha.
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PMID:Increased expression of GAD mRNA during the chronic epileptic syndrome due to intrahippocampal tetanus toxin. 139 47

How seizures spread during epileptiform events has been the subject of intensive investigation over the years. The present study explored the relationship between the amygdala and the hippocampus during afterdischarges. Stimulating electrodes were placed in the amygdala and CA3 regions on the left side in urethane-anesthetized rats. Recording microelectrodes were placed in the dentate gyrus on the left and the CA1 cell layer on the right. Afterdischarges were elicited by stimulus trains between 10 and 50 Hz to the amygdala. Most of the afterdischarges consisted of broad positive potentials in dentate gyrus and no shift of the DC potential. When the stimulus trains were repeated, the afterdischarge evolved, first by spreading to the contralateral side and then by the appearance of maximal dentate activation. The onset of maximal dentate activation was indicated by the appearance of bursts of large amplitude population spikes and a negative shift of the DC potential. These data demonstrate that two types of afterdischarges can be produced in the hippocampus of the anesthetized rat after amygdala stimulation. The observations support the hypothesis that maximal dentate activation represents synchronized reverberatory activity throughout the hippocampal-parahippocampal circuit and indicate that amygdala stimulation can access this circuit in the anesthetized animal.
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PMID:Amygdala stimulation produces two types of hippocampal afterdischarges in the urethane-anesthetized rat. 144 21

Ovarian steroids modulate learning, memory, and epileptic seizure activity, functions that are mediated in part by the hippocampus. Normal function depends on precise interactions between the inhibitory gamma-aminobutyric acid (GABA)ergic and excitatory glutamatergic neurons of the hippocampus. To determine whether estradiol and progesterone interact with GABAergic neurons, the levels of mRNA for glutamic acid decarboxylase (GAD), the rate-limiting enzyme for GABA synthesis, were measured by in situ hybridization histochemistry with 35S-labeled riboprobes complimentary to the feline GAD cDNA. The levels of mRNA for GAD were analyzed in selected region of the dorsal hippocampus and medial basal hypothalamus in ovariectomized, ovariectomized estradiol-treated, and ovariectomized estradiol- and progesterone-treated rats. In estradiol-treated rats, GAD mRNA levels increased in GABAergic neurons associated with the CA1 pyramidal cell layer, but not in the stratum oriens of CA1 or any other region of the hippocampus. Estradiol plus progesterone treatment reversed the estradiol-induced increase in GAD mRNA in CA1 and induced a small decrease in the hilus. No effect of estradiol or progesterone was observed in the dorsomedial, ventromedial, or arcuate nuclei of the hypothalamus. Estradiol or progesterone may alter cognitive performance and seizure activity by increasing or decreasing, respectively, the activity of GABAergic neurons in the hippocampus.
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PMID:Glutamic acid decarboxylase messenger ribonucleic acid is regulated by estradiol and progesterone in the hippocampus. 144 11

Effects of loreclezole (R72063), a triazole derivative with anticonvulsant properties, were studied on field potentials in rat hippocampal slices and on different patterns of low Mg(2+)-induced epileptiform activity in combined entorhinal cortex-hippocampal slices. Lowering extracellular Mg2+ induced recurrent (10-60/min), short (40-80 ms) discharges in hippocampal areas CA1 and CA3. In the entorhinal cortex (EC) up to 90 s long ictaform events associated with large negative field potential and changes in the neuronal microenvironment were generated. These seizure like events changed their characteristics after one to two hours to recurrent discharges of 0.8 to 10 s. 20 microM loreclezole blocked the seizure like events in the entorhinal cortex completely 30-80 min after onset of application. The recurrent short discharges in the hippocampus were reliably blocked by 40 muM loreclezole 60-90 min after bath application with incomplete recovery after washout of several hours. The recurrent discharges in the entorhinal cortex were reliably blocked by 80 microM loreclezole applied for 80-100 min. Decreases in [Ca2+]o and associated slow field potentials evoked by repetitive stimulation of the stratum radiatum were depressed in a dose dependent manner, while similar changes induced by alvear stimulation remained almost unaffected. A paired pulse stimulus paradigm used to test for effect of loreclezole on synaptically evoked transient field potentials in normal medium revealed interference with mechanisms involved in frequency potentiation. While responses to alvear stimulation were largely unaffected, the response to a paired pulse stimulus to stratum radiatum was depressed over the whole range of tested stimulus intervals (15 to 150 ms). The findings suggest that loreclezole has effects on different patterns of epileptiform activity induced by extracellular low Mg2+ possibly by interfering with processes leading to frequency potentiation.
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PMID:Effects of the triazole derivative loreclezole (R72063) on stimulus induced ionic and field potential responses and on different patterns of epileptiform activity induced by low magnesium in rat entorhinal cortex-hippocampal slices. 147 Feb 29

Fifty-nine patients with temporal-lobe epilepsy (28 left, 31 right) completed the Boston Naming Test (BNT), verbal subtests of the Wechsler Adult Intelligence Scale-Revised, and the Logical Memory Subtest of the Wechsler Memory Scale (WMS) before surgery. Performances by patients with left temporal seizure foci were significantly more impaired than those of patients with right seizure foci on the WMS Logical Memory subtest and the BNT. After surgical removal of the mesial temporal lobe structures, two blinded observers established volumetric cell densities for hippocampal subfields CA1, CA2, CA3, the hilar area, and the granule cell layer of area dentata. Statistically significant correlations existed only between percent retention scores and hippocampal neuron loss in CA3 and the hilar area for patients with left temporal seizure foci. None of the other dependent measures was significantly correlated with hippocampal neuron density in any subfield. These results support the hypothesis that certain verbal memory impairments are attributable to hippocampal damage specifically, and not to temporal lobe damage in general.
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PMID:Specificity in the correlation of verbal memory and hippocampal neuron loss: dissociation of memory, language, and verbal intellectual ability. 147 37

Extracellular acetylcholine (ACh) levels were determined, by intracranial microdialysis, in medial septum, amygdala and hippocampus (CA1, CA3, dentate gyrus) of rats during seizures induced by systemic administration of soman (pinacolyl methylphosphonofluoridate), a potent inhibitor of acetylcholinesterase (AChE). In all septo-hippocampal areas a two phase variation was observed: a primary increase in ACh during the pre-seizures period, followed by a decline after 10 to 20 min of seizures and then a second release at 50 min of seizures. In amygdala a progressive increase of the ACh level reached a maximal value at 50 min. ACh levels than returned to basal values in all areas. Hippocampal AChE activity remained totally inhibited throughout the experiment. Possible dynamic phenomena underlying these variations (blood-brain barrier opening, autoregulation of release) are suggested. The present results are compared to previous reports about glutamate changes in the same areas during soman seizures. This comparison gives evidence that in septo-hippocampal areas the glutamatergic system is recruited after an early accumulation of extracellular ACh. The respective roles of ACh and glutamate in triggering and maintenance of soman seizures activity are discussed.
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PMID:Extracellular acetylcholine changes in rat limbic structures during soman-induced seizures. 147 60

Experimental studies have shown that seizure manifestations vary as the brain develops. This study investigated the characteristics of afterdischarges in the hippocampal circuits at various ages in the developing rat. Rats from the following post-natal periods were tested: PN 10-11, PN 14-15, PN 17-19, PN 21-23 and PN 25-27. Animals were anesthetized with urethane and recording electrodes placed in the hippocampus bilaterally. Stimulating electrodes were placed in the left CA3 region and in the angular bundle. Afterdischarges were produced in all animals using stimulus trains of 20 or 50 Hz. Rats in the PN 10-11 and 14-15 age groups had afterdischarges that consisted of population spikes in CA1 and broad positive potentials in the dentate gyrus. Between PN 17 and 19, maximal dentate activation, which consists of bursts of large amplitude population spikes in the dentate gyrus, first appeared in response to 20 Hz stimulation to CA3 or either 20 or 50 Hz stimulation to the angular bundle. Rats older than 21 days had afterdischarge patterns like those recorded in the adult. These data indicate that, in the rat, the seizure capabilities of the limbic circuits go through a major transition period around PN 17-19. The appearance of maximal dentate activation marks the ability of the developing rat brain to produce and sustain reverberatory seizure discharges.
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PMID:Ontogeny of hippocampal afterdischarges in the urethane-anesthetized rat. 147 56


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