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

Kainic acid, an analog of the excitatory amino acid L-glutamate, induces acute hyperexcitability and permanent structural alterations in the hippocampal formation of the adult rat. Administration of kainic acid is followed by acute seizures in hippocampal pathways, neuronal loss in CA3 and the hilus of the dentate gyrus, and reorganization of the synaptic connections of the mossy fiber pathway. Rats with these hippocampal structural alterations have increased susceptibility to kindling. To evaluate the role of the acute seizures and associated hippocampal structural alterations in the development of this long-lasting susceptibility, rats that received intraventricular kainic acid were cotreated with phenobarbital (60 mg/kg, s.c., once daily). Treatment with this dose for 5 d after administration of kainic acid suppressed acute seizure activity, protected against excitotoxic damage in the dentate gyrus, reduced mossy fiber sprouting, and completely abolished the increased susceptibility to kindling associated with kainic acid. Brief treatment with phenobarbital modified the pattern of damage and synaptic reorganization in the dentate gyrus in response to seizure-induced injury, and altered the long-lasting functional effects associated with hippocampal damage. As phenobarbital treatment did not protect against neuronal damage in CA3 or other regions of the hippocampus, the circuitry of the dentate gyrus was implicated as a locus of cellular alterations that influenced the development of kindling. These observations are evidence that pharmacological intervention can prevent the development of epilepsy in association with acquired structural lesions, and suggest that pharmacological modification of cellular responses to injury can favorably alter long-term functional effects of CNS damage.
 ...
PMID:Alteration of long-lasting structural and functional effects of kainic acid in the hippocampus by brief treatment with phenobarbital. 143 95

In order to understand the mechanisms underlying the seizure generation, the present study has investigated the effect of hypoxia on the transition between seizure and interictal bursting. Bathing rat brain slices of the hippocampus and entorhinal cortex in magnesium-free medium elicits electrographic seizures. However, they are eventually replaced by the interictal bursts. It has previously been shown that the interictal bursts, arising in the hippocampal area CA3, are propagated to and disrupt the seizure generation in the entorhinal cortex. In this report we demonstrate that hypoxia promotes the seizure reappearance in the entorhinal cortex by suppressing the interictal bursts in CA3.
 ...
PMID:The effect of hypoxia on the epileptiform activities induced by magnesium-free medium in rat brain slices. 143 63

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.
 ...
PMID:Amygdala stimulation produces two types of hippocampal afterdischarges in the urethane-anesthetized rat. 144 21

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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:Ontogeny of hippocampal afterdischarges in the urethane-anesthetized rat. 147 56

The behavioural and neuropathological effects of both systemic and intrahippocampal injections of paraquat dichloride (1,1'-dimethyl 4,4'-bipyridinium dichloride) were studied in rats. Paraquat (0.1-1.0 mumol) injected into the dorsal hippocampus, produced limbic motor seizures within a few minutes of injection followed by neuronal damage in the CA1 and CA3 pyramidal cell layers, pyriform cortex, dentate granule cell layer and in the hilus fascia dentata at 24 hr (n = 9 rats). A smaller dose of paraquat (10 nmol) was ineffective. The effects of intrahippocampal injections of paraquat (1 mumol) were prevented by administering it together with atropine (50 nmol; n = 6 rats) or by giving it 60 min. after MK 801 (0.3 mg.kg-1 intraperitoneally). Systemic injections of paraquat (20-100 mg.kg-1) also produced forelimb clonus and rearing in 10 out of 15 animals. Neuronal cell death was found 24 hr later in 9 of these rats and was restricted to the pyriform cortex, the brain region with the highest concentrations of paraquat. Atropine (150 mg.kg-1 intraperitoneally given 60 min. previously) completely prevented the motor seizures but cell death still occurred in 2 of the 6 animals tested. In conclusion, both systemic and intrahippocampal injections of paraquat produced behavioural excitation accompanied 24 hr later by brain damage and antagonist studies suggested involvement of muscarinic and NMDA receptors in the neurotoxic mechanism.
 ...
PMID:Production of limbic motor seizures and brain damage by systemic and intracerebral injections of paraquat in rats. 148 May 53

1. Subcutaneous kainate injection in rats evoked acute seizures and led to cell loss in the hilus and areas CA1 and CA3, which resembled the pattern of hippocampal sclerosis often associated with temporal lobe epilepsy in humans. 2. Simultaneous intra- and extracellular recordings were performed in the stratum pyramidale of area CA1 while stimulating in the stratum radiatum close to the recording electrodes. Responses from control slices consisted of a brief excitatory postsynaptic potential (EPSP) with only one action potential, corresponding to a single extracellular population spike, followed by a clear biphasic inhibitory postsynaptic potential (IPSP). In slices from kainate-treated animals, however, stimulation evoked a prolonged EPSP, which often triggered multiple action potentials corresponding to multiple extracellular population spikes. 3. In slices from kainate-treated animals, the mean amplitude but not the duration of the stimulation-evoked IPSP was reduced. The extent of the kainate-induced loss of inhibition in area CA1 was highly variable. 4. Low concentrations of bicuculline in control slices led to a moderate hyperexcitability, which consisted of multiple population spikes and mirrored the responses observed in slices from kainate-treated animals in normal ACSF. Prolonged application of 10-30 microM bicuculline for > or = 30 min led to a much higher level of hyperexcitability, which was similar in slices from controls and kainate-treated rats. These findings are consistent with the hypothesis that the hyperexcitability of CA1 pyramidal neurons following kainate treatment is mainly due to decreased GABAA-receptor-mediated inhibition and that the loss of inhibition is only partial.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Persistent hyperexcitability in isolated hippocampal CA1 of kainate-lesioned rats. 149 Dec 62

Low doses of quinolinic acid (QUIN) administered intracerebroventricularly (ICV) to rats produced either no damage or mild to moderate damage in the pyramidal cell layer of the hippocampus and resulted in mild, limbic seizures in the majority of animals treated. The same dose of QUIN following ICV pretreatment with the nitric oxide synthase inhibitor N-nitro-L-arginine (NARG), produced extensive hippocampal lesions with complete loss of the pyramidal layer in 50% of the animals, and moderate damage with total neuronal loss in areas CA1 and CA3 in the remainder of the group. Animals treated with both NARG and QUIN also exhibited a greater incidence of severe convulsive behavior (9/11) and 3 deaths. Pretreatment with the nitric oxide-generating drug molsidomine attenuated the enhanced toxicity observed with combined NARG-QUIN treatment, resulting primarily in no detectable hippocampal damages and mild seizures resembling those produced by QUIN alone. Administration of NARG alone produced neither seizure activity nor histological evidence of neurotoxicity. We conclude that inhibition of nitric oxide production with NARG potentiates the neurotoxicity of quinolinic acid in the rat hippocampus.
 ...
PMID:Potentiation of quinolinate-induced hippocampal lesions by inhibition of NO synthesis. 149 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>