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

The present study compares the efficacy of carbamazepine (20 mg/kg/day) and vigabatrin (250 mg/kg/day) in preventing hippocampal and amygdaloid damage in the perforant pathway stimulation model of status epilepticus in the rat. One group of rats received a combination of the drugs. Drug treatments were started one week before the stimulation and continued for two weeks thereafter. Gallyas silver impregnation and somatostatin immunohistochemistry were used to detect neuronal damage. All drug treatments were equally effective in decreasing the number and severity of seizures during electrical stimulation. In the vigabatrin group, the damage to the hilar somatostatin-immunoreactive (SOM-ir) neurons and hippocampal CA3c pyramidal cells was less severe than in the vehicle (SOM-ir, P < 0.01; CA3c, P < 0.05) and carbamazepine (SOM-ir, P < 0.01; CA3c, P < 0.05) groups. In the carbamazepine and combination groups, the severity of neuronal damage in the hippocampus did not differ from that in vehicle-treated animals. The amygdaloid neurons were not protected by any of the treatments. Our results show that even though vigabatrin and carbamazepine treatments had similar anticonvulsant efficacy during the perforant pathway stimulation, only vigabatrin but not carbamazepine decreased seizure-induced neuronal damage. Vigabatrin decreased neuronal damage in the hippocampus but not in the amygdala. These results demonstrate that different brain regions and neuronal networks may be protected unequally by different anticonvulsants.
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PMID:Vigabatrin and carbamazepine have different efficacies in the prevention of status epilepticus induced neuronal damage in the hippocampus and amygdala. 880 Jun 33

The issue of whether neuronal degeneration is a primary factor in activation of astrocytes during epileptogenesis was addressed using the kindling model of epilepsy. No degenerative changes specific to the kindling process were observed in brain sections from kindled animals, sampled from the olfactory bulbs through to cerebellum and processed with the degeneration-sensitive cupric silver stain. Also, examination of lectin-stained sections did not reveal any reactive microglia. At the same time, reactive astrocytes, as judged by an increase in glial fibrillary acidic protein immunoreactivity and a de novo vimentin immunoreactivity, were prominent in amygdala, piriform cortex, entorhinal cortex and hippocampus. These results suggest that loss of neurones is not a prerequisite for establishment of epilepsy-prone state, that seizures of short duration do not necessarily result in neuronal death, and that in kindling, astrocytes are activated by factors that are not related to neuronal degeneration, but which are likely associated with abnormal neuronal activity.
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PMID:Activation of astrocytes during epileptogenesis in the absence of neuronal degeneration. 898 6

It is still a question of much debate whether single epileptic seizures can cause cell loss. Despite the clinical impression that epilepsy in general is a progressive disorder, experimental evidence is not conclusive on this point. Recently, it has been shown that electrically-induced afterdischarges of less than 2 min may induce structural impairments in neurons. Here we evaluated whether spontaneous seizures would lead to similar impairments. Chronic spontaneous recurrent seizures were induced with pilocarpine (320 mg/kg, i.p.). Animals were sacrificed from 1 to 6 h either after single or multiple seizures. A Golgi-like sensitive silver-impregnation procedure was used to reveal injured neurons. Silver-impregnated dark neurons were never found in control animals nor in epileptic animals that had no behavioral seizures in the 8 h prior to sacrifice. After spontaneous seizures (injured) dark neurons were mostly interneurons and were present in hippocampus (CA1 stratum radiatum), amygdala, piriform cortex and other limbic structures. Animals with multiple seizures had a higher number of dark cells than animals with single seizures. Our findings suggest that even single generalized spontaneous tonic-clonic seizures can induce long-lasting morphological changes. Our results favor the idea that epilepsy is a progressive disorder where one seizure begets the next.
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PMID:Spontaneous seizures preferentially injure interneurons in the pilocarpine model of chronic spontaneous seizures. 898 94

Kainic acid-induced seizures, in adult rats produce neurodegeneration in the hippocampus followed by sprouting of the mossy fibres in the inner molecular layer of the dentate gyrus and changes in GAP-43 expression in the granule cells. In the present study we observed that 4 days after kainic acid injection a dense plexus of silver-impregnated degenerating terminals detected by Gallyas's method and a decrease of GAP-43 immunostaining was observed in the inner molecular layer of the dentate gyrus indicating deafferentiation of this region. This was associated with the formation of an intense GAP-43 immunostained band in the supragranular layer. MK-801, a non-competitive inhibitor of the NMDA receptor, which partially inhibited the behavioural seizures induced by KA, also protected from the inner molecular layer deafferentation and markedly reduced the expression of GAP-43 mRNA in the granule cells and the intense GAP-43 immunostained band in the supragranular layer, suggesting a relationship among these events. Two months after kainic acid injection the intense supragranular GAP-43 positive band was no longer evident but the whole inner molecular layer appeared more labelled in association with the formation of the collateral sprouting of the mossy fibres in the inner molecular layer as detected by Timm's staining. These effects were also markedly reduced by the pretreatment with MK-801. Taken together, these experiments indicate for the first time a direct relationship between the increase of GAP-43 immunostaining in the inner molecular layer of the dentate gyrus and the collateral sprouting of mossy fibres in this district in response to kainic acid induced seizures. This further supports the hypothesis that the early induction of GAP-43 in granule cells may be one of the molecular mechanisms required for the synaptic reorganization of the mossy fibres.
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PMID:Relationship between GAP-43 expression in the dentate gyrus and synaptic reorganization of hippocampal mossy fibres in rats treated with kainic acid. 904 73

Domoic acid induces a time-dependent neuroexcitotoxic effect in neonatal rats characterized by hyperactivity, stereotypic scratching, convulsions, and death with observable behaviors occurring at exposures 40 times lower by body weight in neonates than reported in adults. Low doses of domoic acid (0.1 mg/kg) induced c-fos in the central nervous system which was inhibited in part by 2-amino-5-phosphonovaleric acid, an NMDA receptor antagonist. Domoic acid caused no evidence of structural alteration in the brain of neonates as assessed by Nissel staining and cupric silver histochemistry. Domoic acid induced reproducible behavioral effects at doses as low as 0.05 mg/kg and induced seizures doses as low as 0.2 mg/kg. Determination of serum domoic acid levels after 60 min exposure indicated that serum levels of domoic acid in the neonates corresponded closely to the serum levels that induce similar symptoms in adult rats and mice. We conclude that neonatal rats are highly sensitive to the neuroexcitatory and lethal effects of domoic acid and that the increased sensitivity results from higher than expected serum levels of domoic acid. These findings are consistent with other findings that reduced serum clearance of domoic acid is a predisposing factor to domoic acid toxicity.
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PMID:Domoic acid is a potent neurotoxin to neonatal rats. 913 93

The study was designed to determine which type of cell death occurs following kindling induced seizures, and to determine which neurons die. For this purpose seizures were kindled from the entorhinal cortex. Following a range of 5-85 stage 5 seizures, rats were sacrificed, and the tissue was prepared for analysis. The TUNEL and silver impregnation methods were used to identify apoptotic or necrotic cell death, respectively. These methods were subsequently combined with immunocytochemistry, to determine if diseased neurons expressed somatostatin or the NMDA receptor (NMDAR1). The tissue analysis demonstrated that following kindling induced seizures, 1) hippocampal and extrahippocampal neurons die, 2) some neurons die through apoptosis, others through necrosis, and 3) some of the diseased neurons express somatostatin, others the NMDAR1 and that both subpopulations of neurons are present at hippocampal and extrahippocampal sites.
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PMID:Apoptotic and necrotic cell death following kindling induced seizures. 915 Jul 99

To examine the relationship between cell death and sprouting of the mossy fibers, repeated seizures of the hippocampal-parahippocampal circuit were elicited in anesthetized rats. The presence of mossy fiber growth was assessed with the Timm's stain for zinc. At 4 weeks, after 18 repeated seizures, there was a significant increase in the degree of zinc containing granules in the inner molecular layer of the dentate gyrus. The amount of sprouting was less than that seen four weeks after a single injection of kainic acid. A silver impregnation stain and an assay for damaged DNA were used to detect damaged or dying neurons and immunohistochemistry for a 72 kDa heat shock protein was used to detect any neurons that had suffered potentially injurious stress. The same number of repeated seizures that caused sprouting of the mossy fibers did not cause detectable cell death or severe stress in any cells within the hippocampus, subicular region or adjacent entorhinal cortex. These experiments demonstrate that repeated seizures of the hippocampal-parahippocampal circuits can cause sprouting of mossy fibers in the absence of evidence of cell death. This supports the hypothesis that alterations in intrinsic neural excitability and impulse activity from the dentate gyrus can result in growth of axonal processes in the adult rat brain.
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PMID:Is cell death necessary for hippocampal mossy fiber sprouting? 916 92

Neonatal seizures in the neonatal period are symptoms of numerous underlying disorders of the neonate. We present a case in which neonatal seizures due to cerebral infarction led to a diagnosis in the mother. Neonatal convulsions caused by cerebral artery thrombosis is relatively rare in the neonatal period and is often secondary to indwelling intravascular catheters that cause thromboembolism, but may be associated with many conditions.1 Cerebral artery thrombosis in newborns, in which antiphospholipid antibodies (APA) were found in the mother, has been described in three case reports. Two of these premature infants were born with other risk factors for thrombosis. APA could not be identified in any of these three infants. In the two cases reported by Silver et al the diagnosis was made several months after birth. This case is unique in the fact that no other risk factors for thrombosis could be identified to explain the infarction, and that APA were found in the offspring of an apparently healthy mother. Whether the prior fetal death was caused by APA remains unclear. The finding of lupus anticoagulant in her child led to the diagnosis of antiphospholipid antibody syndrome in her. We believe that in case of cerebral artery thrombosis in a neonate, with no trivial cause such as an indwelling catheter or sepsis, both mother and infant should be tested for presence of APA, even when the mother seems healthy.
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PMID:An unusual cause of neonatal seizures in a newborn infant. 931 May 41

In adult rats, kainic acid-induced status epilepticus markedly reduces GluR2 (the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid, AMPA subunit that limits Ca2+ permeability), receptor mRNA in the vulnerable CA3 and may contribute to delayed neurodegeneration. In rat pups resistant to kainate seizure-induced hippocampal neurodegeneration by silver impregnation, glutamate or GABA(A) alpha1-receptor mRNAs were unaltered in CA3 neurons 24 h after status epilepticus. In the dentate gyrus, GluR1 and GluR2 mRNAs were transiently increased in P14 but not P5 pups. Immunocytochemistry revealed no apparent differences in the distribution patterns of GluR1, GluR2, or GluR2/3 receptor proteins in the CA3 or dentate gyrus of P14 pups. Status epilepticus-induced alterations in receptor GluR2 and GABA(A) alphal mRNAs and AMPA protein expression vary with developmental age. Sustained expression at young ages may contribute to the resistance of developing hippocampal neurons to seizure-induced damage.
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PMID:Developmental regulation of glutamate and GABA(A) receptor gene expression in rat hippocampus following kainate-induced status epilepticus. 944 90

In rats, most neurons in layer III of the medial entorhinal cortex are exquisitely vulnerable to prolonged seizure activity. These neurons have also been shown to die preferentially in the entorhinal cortex of patients with temporal lobe epilepsy. This lesion can be duplicated in rats by a focal injection of the indirect excitotoxin aminooxyacetic acid into the entorhinal cortex. The present study was designed to examine the neuropathological consequences of an intra-entorhinal aminooxyacetic acid injection at various time-points with a sensitive silver staining method for the visualization of damaged neurons. After 3 h, affected cells with prominently stained processes were readily observed in the transition zone of the hippocampal CA1 field and the subiculum, but no silver-stained neurons were seen in the entorhinal cortex. Less consistently, damaged neurons were observed in the presubiculum, in the temporal and perirhinal cortices and in the lateral amygdaloid nucleus. At 6 h after an aminooxyacetic acid injection, numerous silver-stained neurons, which were typically devoid of processes, were also seen in layer III of the medial entorhinal cortex. This pattern of neurodegeneration remained similar at 12 and 24 h following the aminooxyacetic acid injection, though many silver-stained neurons were noted in layer II of the lateral entorhinal cortex as well. Notably, at five days, silver-stained neurons had disappeared. Instead, dendritic arbors, debris of degenerated neurons and reactive glial cells were present in lesioned brain regions. These data demonstrate the chronology and the extent of neuronal damage following an intra-entorhinal injection of aminooxyacetic acid. The results suggest that a detailed examination of the temporal sequence of neuronal death in the entorhinal cortex and in extra-entorhinal areas is likely to benefit our understanding of the pathophysiology of temporal lobe epilepsy.
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PMID:Neuronal damage after the injection of aminooxyacetic acid into the rat entorhinal cortex: a silver impregnation study. 946 38


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