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

High amplitude spiking representative of seizures, accompanied by an unusual motor behavior pattern of rearing and forelimbic clonus resembling "boxing," was elicited by microinjection of the cholinergic agonist, carbachol, 4 micrograms, into the medial prefrontal cortex of the rat. A rating scale devised to score the behavior revealed a motor pattern elicited by carbachol from the medial anterior cortex which was similar to that described by Racine for electrical stimulation of the amygdala. Topographical analysis of the areas surrounding the medial anterior cortex region revealed that the motor manifestations of seizures were elicited over a wide region of the anterior cortex, with scores significantly lower at carbachol microinjection sites greater than 1 mm rostral, 2 and 3 mm caudal, and 2 mm lateral to the standard medial prefrontal cortex site. Unilateral microinjection of carbachol yielded motor seizures primarily from the contralateral forepaw, suggesting involvement of a crossed pathway. Retrograde tracing with fast blue dye, combined with immunostaining for choline acetyltransferase and NADPH-diaphorase, found that the cholinergic neurons innervating the standard microinjection site were the dorsolateral tegmental cells, as previously reported, which have been shown to also contain substance P and corticotropin releasing factor. In addition, cholinergic neurons of the nucleus basalis of Meynert region were found to innervate the standard microinjection site. These findings implicate cholinergic innervation of the rostral cortex in classical limbic seizures.
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PMID:Anatomical analysis of frontal cortex sites at which carbachol induces motor seizures in the rat. 317 34

Lesions of the nucleus basalis magnocellularis and the medial septal area have been shown to produce both deficits in memory and decreases in choline acetyltransferase levels. In order to determine whether functional changes in acetylcholine receptor sensitivity also occur, the present experiment examined the ability of acetylcholine, 40 micrograms intraventricularly, to induce motor seizures in nucleus basalis magnocellularis-medial septal area lesioned versus control rats. While choline acetyltransferase activity was only modestly reduced in lesioned rats vs control rats (30%), the seizure scores were considerably higher in lesioned vs. control rats (270%). These results suggest that there is an increased functional response to acetylcholine following bilateral nucleus basalis magnocellularis-medial septal area lesions.
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PMID:Behavioral evidence for increased acetylcholine receptor sensitivity after nucleus basalis magnocellularis lesions in the rat. 318 Dec 90

The development of kindled seizures elicited through electrical stimulation of the rat olfactory bulb (OB) was examined under two conditions which decrease cholinergic neurotransmission. Atropine sulfate (25 mg/kg, IP) administered 1 hr prior to stimulation of the OB was found to significantly delay the acquisition of the fully kindled state. In a second experiment, diminished cholinergic innervation of the OB was established using chemical lesions of the basal forebrain cholinergic system. Despite the depletion of acetylcholine (Ach), as determined by acetylcholinesterase (AchE) and choline acetyltransferase (ChAt) assays, no significant alterations in kindling parameters were observed. Based upon these findings we suggest that Ach is not critical to the establishment of an OB kindled focus but is important for the propagation and generalization of epileptiform activity initiated through OB stimulation.
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PMID:Atropine slows olfactory bulb kindling while diminished cholinergic innervation does not. 337 May 4

We have assessed the relative neurochemical effects of valproic acid, ethosuximide, and diazepam on dissociated cultures of mouse cerebral cortex. Cultures were exposed chronically (11 days) to each antiepileptic drug and assayed for number of neurons, total protein, tetanus toxin fixation, high-affinity uptake of gamma-aminobutyric acid and beta-alanine, choline acetyltransferase activity, and specific and clonazepam-displaceable benzodiazepine binding. Ethosuximide-exposed cultures did not evidence neuronal toxicity; exposure to valproic acid and diazepam resulted in modest neuronal toxicity. However, exposure to each of these drugs resulted in a marked reduction in benzodiazepine binding. This effect may relate to a common mechanism of action of drugs used to treat absence seizures.
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PMID:Differential neurochemical effects of chronic exposure of cerebral cortical cell culture to valproic acid, diazepam, or ethosuximide. 393 44

Behavioural, neurochemical and histopathological changes induced by systemic injection of kainic acid were investigated at various doses of the neurotoxin (3, 6 and 10 mg/kg s.c.). There was a positive correlation between the dose of kainic acid and the extent of both the acute neurochemical changes 3 h after the injection (increases of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid levels and a decrease in noradrenaline levels in all brain regions investigated), the acute histopathological changes (shrinkage and condensation of nerve cells and brain oedema in the entire forebrain) and the extent of behavioural alterations (immobility, 'wet dog shakes' and limbic seizures). However, the slope of the dose-response curves was very steep. Late and irreversible alterations included losses of the enzyme markers glutamic acid decarboxylase and choline acetyltransferase and, histopathologically, incomplete parenchymal necrosis and haemorrhages. These changes, however, were restricted to a few brain regions, the most important being the hippocampus, amygdala, entorhinal and pyriform cortex, and olfactory bulb, and they were seen only in animals which had undergone severe convulsions. It is suggested that the irreversible brain lesions in this animal model of limbic (temporal lobe) epilepsy are not solely induced by a direct action of kainic acid, but may be caused--at least in part--by additional, secondary pathogenetic mechanisms.
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PMID:Kainic acid-induced seizures: dose-relationship of behavioural, neurochemical and histopathological changes. 402 98

The ability of three derivatives of folic acid, N-5-methyltetrahydrofolic acid (MTHF), tetrahydrofolic acid (THF) and dihydrofolic acid (DHF) to mimic the actions of kainic acid (KA) in a number of in vitro and in vivo systems known to be sensitive to KA was examined. None of the three folate derivatives at 100 microM concentration significantly inhibited the specific binding of [3H]-KA to striatal membranes although 2 microM L-glutamate produced a 40% inhibition. None of the three folate derivatives stimulated the formation of cyclic GMP in cerebellar slices incubated in vitro although KA (0.5 mM) increased cyclic GMP levels by 2.5-fold. Whereas intrahippocampal injection of 2.3 nmoles of KA produces prolonged abnormalities of the EEG, limbic-type seizures and a characteristic pattern of neuronal degeneration in the hippocampal formation and related structures, intrahippocampal injection of a 100-fold greater dose of THF caused only minor and transient EEG abnormalities, no overt seizures and a highly restricted lesion. Whereas intrastriatal injection of 5.6 nmoles of KA caused a profound reduction in the specific activities of choline acetyltransferase and glutamate decarboxylase, markers for striatal intrinsic cholinergic and GABAergic neurons, 50-fold greater doses of MTHF did not affect either enzyme although this high dose of THF did cause a significant 33% reduction in choline acetyltransferase activity. These findings support the suggestion that THF may have weak neurotoxic effects in brain but indicate that the actions of this compound and the related MTHF and DHF are not mediated through KA-specific receptors.
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PMID:Failure of folic acid derivatives to mimic the actions of kainic acid in brain in vitro or in vivo. 612 82

Behavioural, histopathological and neurochemical changes induced by systemic injection of kainic acid (10 mg/kg, s.c.) were investigated in rats. The most pronounced behavioural changes were strong immobility ("catatonia"), increased incidence of "wet dog shakes", and long-lasting generalized tonic-clonic convulsions. The behavioural symptoms were fast in their onset and lasted for several hours. Two distinct phases of histopathological and neurochemical changes were observed. (1) Early partially reversible changes were seen up to 3 h after kainic acid injection. They consisted of shrinkage and pyknosis of neuronal perikarya together with swelling of dendrites and axon terminals. These changes were accompanied by generalized signs of edema throughout the whole brain. Neurochemically, there was a marked decrease in noradrenaline levels (up to 70%) and an increase in levels of 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid and homovanillic acid (up to 200%) in all analysed brain regions, suggesting a strongly increased firing rate of aminergic neurones during the period of generalized seizures. These histological and neurochemical changes were found in all the brain regions examined; they were greatly reduced or only sporadically seen after 1-3 days, when the animals had recovered from the seizures. (2) Late irreversible changes developed 24 h and later following kainic acid injection. They consisted of incomplete tissue necrosis with loss of nerve cells and oligodendrocytes, demyelination, astroglial scar formation, small perivenous hemorrhages and extensive vascular sprouting. The changes were restricted to the pyriform cortex, amygdala, hippocampus (most pronounced in the CA1 sector), gyrus olfactorius lateralis, bulbus olfactorius and tuberculum olfactorium. Neurochemically, a selective decrease was seen in choline acetyltransferase activity (40%) of the amygdala/pyriform cortex area, and of glutamate decarboxylase activity in the dorsal hippocampus (45%) and amygdala/pyriform cortex (55%). No such changes were found in the frontal cortex and the striatum/pallidum. Since at these later time periods the widespread early changes in monoamine metabolism were mostly normalized, loss of acetylcholine and gamma-aminobutyric acid neurons in the affected brain regions represented a selective neurochemical change typical for this stage of kainic acid action. The observed neurochemical and histopathological changes may be directly related to the excitotoxic and convulsive properties of kainic acid. However, brain edema resulting in herniation damage of the basal portions of the brain in addition to disturbances of microcirculation and +
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PMID:Kainic acid induced seizures: neurochemical and histopathological changes. 614 39

The substantia innominata complex (SI) is the major source of cholinergic innervation to the amygdala, entorhinal and pyriform cortices, and the neocortex. Immunohistochemical studies using both monoclonal and polyclonal antibodies to choline acetyltransferase (ChAT) have clearly identified that the large size neurons of this area are cholinergic. We have lesioned this area by three methods: electrocoagulation, kainic acid (KA) injection and folic acid (FA) injection. Biochemical (GAD, ChAT and QNB binding) and histological studies of the SI and its known target areas as well as the hippocampus, thalamus and striatum were undertaken. Histologically, electrolytic and KA (2 nmol) lesions produced extensive local damage, but local damage was minimal with FA (100-250 nmol). Electrolytic lesions produced no remote neuronal damage. KA injections produced mild to moderate damage in the amygdala and cortex, while FA produced severe damage in the amygdala and pyriform cortex, with less severe damage in the entorhinal cortex and neocortex. Biochemically, electrolytic lesions produced drops in ChAT only in remote areas. Kainic acid produced moderate drops in ChAT, GAD and QNB binding. FA, on the other hand, produced only a minimal change in ChAT, but very heavy reductions in GAD and QNB binding. Thus, GABA neurons of the cortex were damaged. They may also be the cholinoceptive neurons that were damaged. The remote damage following KA and, particularly, FA, is presumed to be due to the epileptiform activity induced by the local injection of these agents. Reduction in both seizures and remote damage was brought about by pre-treatment of the animals with valium (20 mg/kg) or scopolamine (50 mg/kg). Injection of FA into the amygdala or striatum produced some remote damage but it was much less in magnitude than after SI injection.
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PMID:A possible relationship between folic acid neurotoxicity and cholinergic receptors in the pyriform cortex and amygdala. 657 18

Injection of a few nanomoles of the muscarinic agonists carbamylcholine, muscarine or (+)-acetyl-beta-methylcholine once a day into the rat amygdala was initially subconvulsive, but on repetition led to the progressive development of kindled epileptic seizures. This behaviour was stereospecific, was potentiated by the cholinesterase inhibitor physostigmine, and was blocked by the muscarinic antagonists atropine, QNB and scopolamine. The kindling potencies of cholinergic muscarinic agonists and antagonists paralleled their relative affinities for muscarinic receptors in vitro. No changes in muscarinic receptors, in cholinesterase or in choline acetyltransferase were observed in kindled brains after a stimulation-free period of at least 1 week. These data support the aggregate hypothesis of epileptogenesis and suggest that abnormal activity through a particular group of muscarinic synapses can be sufficient to generate an epileptic focus.
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PMID:Kindling: a pharmacological approach. 696 22

The neurotoxic and convulsant properties of conformationally restricted and synthetic analogues of excitatory acidic amino acids were examined after stereotaxic injection into the striatum and the dentate gyrus of the hippocampal formation. In the striatum, neurotoxicity was quantified by the reduction in the activity of choline acetyltransferase and glutamate decarboxylase, markers for striatal intrinsic neurons. The following sequence of neurotoxic potencies was defined; kainic acid approximately equal to domoic acid much greater than alpha-keto kainic acid approximately equal to alpha-allo kainic acid greater than ibotenic acid approximately equal to cis-cyclopentyl glutamic acid greater than quisqualic acid approximately equal to N-methyl-D-aspartic acid. When normalized for neurotoxic potencies, a wide variation in the convulsant effects of the agents was observed after hippocampal injection. N-Methyl-D-aspartate produced nearly continuous electroencephalographic seizures for 2 hr after injection, where alpha-keto-kainate and kainate and quisqualate caused seizure activity for 64 and 45% respectively of this period; kainate, alpha-allo kainate and domoate caused intermittent seizure activity during approximately 30% of the recording period; ibotenate and cyclopentylglutamate had minimal convulsant effects. Seizures were associated with a significant reduction in the levels of norepinephrine and with increases in the levels of 5-hydroxyindoleacetic acid in the cortex and hippocampal formation and increases in the levels of gamma-aminobutyric acid in the hippocampal formation. Kainate, domoate, keto-kainate and alpha-allo-kainate caused extensive lesions of the hippocampal formation that also involved the pyriform cortex; ibotenate and cyclopentylglutamate caused uniform but substantial lesions limited to the dentate gyrus, whereas quisqualate and N-methyl-D-aspartate produced small and restricted lesions. The results demonstrate a poor correlation between the neurotoxic and convulsant potencies of these excitatory amino acid analogues and suggest that receptor-specific interactions may account for these disparities.
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PMID:Excitatory amino acid analogues: neurotoxicity and seizures. 706 5


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