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

The distribution of basic fibroblast growth factor (bFGF) mRNA in normal rat forebrain, and the influence of recurrent seizure activity on the expression of this mRNA, was evaluated using in situ hybridization and S1 nuclease protection techniques. In the untreated adult rat, hybridization of 35S-labeled bFGF cRNA densely labeled neurons in a few discrete areas including the tenia tecta, indusium gresium, and hippocampal stratum pyramidale of regions CA2 and rostromedial CA1. Neurons in the prosubiculum and rostromedial dentate gyrus stratum granulosum were lightly labeled. In addition, a diffuse distribution of autoradiographic labeling in areas such as the hippocampal molecular layers, olfactory cortical layer I, and the olfactory nerve layer was suggestive of localization in glial cells. Platinum wire hilar lesions, which did not induce seizures, increased cRNA hybridization in glial cells in primary and secondary areas of degeneration in the ipsilateral hemisphere only; hybridization was not noticeably increased in neurons in these lesion-control rats. Focal stainless-steel wire hilar lesions, which caused recurrent seizures 2-10 h postlesion, induced bilaterally distributed increases in cRNA hybridization in hippocampus, neocortex, olfactory cortex, amygdala, and septum. These seizure-dependent increases in hybridization were evident 6 h postlesion, were maximal from 12 to 24 h postlesion, and declined to near control levels by 4 days. In most regions the elevated hybridization appeared to be associated primarily with astroglia but in experimental seizure rats sacrificed 12 and 24 h postlesion hybridization was also markedly increased in the dentate gyrus granule cells and olfactory cortical neurons. These results demonstrate that recurrent seizures increase bFGF mRNA expression by both forebrain neurons and glia and implicate bFGF in the coordination of other changes in the biosynthetic activities of forebrain neurons that occur after seizures.
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PMID:Seizures increase basic fibroblast growth factor mRNA in adult rat forebrain neurons and glia. 817 Mar 44

Repeated kindled seizures induce long-lasting physiological and morphological alterations in the hippocampal formation. In the dentate gyrus (DG), the morphological alterations induced by kindled seizures include loss of polymorphic neurons in the hilus, mossy fiber axon sprouting, and synaptic reorganization of the mossy fiber pathway. In this study, quantitative stereological methods were used to determine the distribution and time course of neuronal loss induced by 3, 30, or 150 kindled generalized tonic-clonic seizures in hippocampal, limbic, and neocortical pathways. Neuronal loss was observed in the hilus of the DG and CA1 after three generalized tonic-clonic seizures, and progressed in these sites to 49% and 44% of controls after 150 seizures. Neuronal loss was also observed in CA3, entorhinal cortex, and the rostral endopyriform nucleus after 30 seizures, and was detected in the granule cell layer and CA2 after 150 seizures. There was no evidence of neuronal loss in the somatosensory cortex after 150 seizures. The time course of the neuronal loss demonstrated selective vulnerability of hippocampal neuronal populations to seizure-induced injury, and suggests that even brief seizures may induce excitotoxic injury in vulnerable neuronal populations. Repeated brief seizures induced neuronal loss in a distribution that resembled hippocampal sclerosis, the most common lesion observed in human epilepsy. The results demonstrated that kindling induces alterations in neural circuitry in a variety of locations in the limbic system, and suggest that hippocampal sclerosis may be acquired in human epilepsy as a consequence of repeated seizures.
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PMID:Neuronal loss induced in limbic pathways by kindling: evidence for induction of hippocampal sclerosis by repeated brief seizures. 818 60

Basic fibroblast growth factor promotes the survival and outgrowth of neurons and protects neurons from glutamate mediated excitotoxicity. The present study investigates the effects of kainate-induced epileptic seizures on the cellular expression of basic fibroblast growth factor messenger RNA and protein. Seizures were induced by injection of 12 mg/kg kainic acid. Rats were killed 3 h, 6 h, and 24 h after injection of the drug and analysed by radioactive and non-radioactive in situ hybridization as well as immunohistochemistry for glial fibrillary acidic protein and basic fibroblast growth factor. Radioactive in situ hybridization revealed a fast (6 h), strong (300-400% of control) and widespread increase of basic fibroblast growth factor messenger RNA after kainate-induced seizures. Non-radioactive in situ hybridization using digoxigenin-labeled riboprobes combined with glial fibrillary acidic protein immunohistochemistry showed that basic fibroblast growth factor messenger RNA was markedly increased in astroglial cells throughout the brain. Immunohistochemistry for basic fibroblast growth factor revealed labeling of nuclei in astrocytes in many forebrain areas and in neurons in area CA2 and fasciola cinereum. Kainate markedly increased basic fibroblast growth factor-like immunoreactivity in nuclei of astrocytes in several forebrain areas. This effect peaked 24 h after injection. It is concluded that basic fibroblast growth factor may play a neuroprotective role in kainate mediated excitotoxicity as seen from a massive and widespread astroglial increase in basic fibroblast growth factor messenger RNA and -like immunoreactivity. These effects may, to a large degree, be mediated through the excessive release of endogenous glutamate, induced by the epileptic seizures, leading to activation of glutamate receptors on astroglial cells through volume transmission, i.e. via diffusion of electrochemical signals in the extracellular fluid pathways.
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PMID:Fast and widespread increase of basic fibroblast growth factor messenger RNA and protein in the forebrain after kainate-induced seizures. 830 52

Using in situ hybridization histochemistry concentrations of mRNAs encoding chromogranin A (ChA), carboxypeptidase H (CPH) and peptidylglycine alpha-amidating monooxigenase (PAM) have been investigated in the hippocampus after kainic acid (KA)-induced limbic seizures in the rat. Increased concentrations (by 150%) of ChA and CPH mRNAs were found in the granule cell layer 24 h after KA injection. At the same time PAM mRNA levels were only slightly elevated (by 50%). Whereas the increases in CPH and PAM transcripts were only transient, ChA mRNA concentrations in the granule cell layer were elevated up to 2 months after the initial seizures. In contrast, in the pyramidal cell layers of all hippocampal subfields (CA1 to CA3) ChA mRNA concentrations were significantly reduced (by 40-70%) 1-60 days after KA. PAM and CPH messages were slightly reduced in the pyramidal cell layer of CA1 but not in CA2 and CA3. The experiments demonstrate that KA-induced limbic seizures cause sustained changes in the expression of ChA mRNA. At the same time the expression of two enzymes involved in post-translational processing of neuropeptides, PAM and CPH, becomes only transiently altered. Synthesis of ChA may be regulated differently in the strata granulosum and pyramidale during epileptic seizures.
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PMID:Kainic acid seizures in the rat: differential expression of chromogranin A, carboxypeptidase H and peptidylglycine alpha-amidating monooxigenase in subfields of the hippocampal formation. 831 Aug 14

Embryonic neural tissue was transplanted into previously kindled rats. A thirteen- to fourteen-day embryonic hippocampal cell suspension was grafted in the stratum oriens near the CA2 area of the hippocampus. Almost 80% of the animals had a good recovery and became seizure-free. Injection of neocortical cells or saline did not show any positive effect on the kindling susceptibility. Although 20 day embryonic cell transplantation was also effective, the effect did not last as long as the 13- to 14-day embryonic transplantation. These observations open the possibility that the neural grafts may be used for therapy of medically intractable epilepsies.
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PMID:Effect of embryonic hippocampal transplantation in amygdaloid kindled rat. 845 71

We examined the relationship of preoperative unilateral memory function and quantitative hippocampal histology in patients undergoing anterior temporal lobectomy for the treatment of complex partial seizures. Recognition memory (objects, words, figures) was assessed preoperatively for each hemisphere by the intracarotid amobarbital procedure in 23 patients (mean age at the time of operation, 30.2 yr; standard deviation, 9.2; mean age at the time of seizure onset, 12.3 yr; standard deviation, 8.6) without tumor. Memory scores were the total number of items recognized, adjusted for guessing. Histological examination of the anterior 20 to 30 mm of hippocampal tissue was accomplished in all patients. The degree of unilateral memory impairment ipsilateral to the seizure focus was significantly correlated with decreased neuronal density in the hilar (r = 0.66, P < 0.001) and dentate granule (r = 0.61, P < 0.002) regions, but not in the CA1 (r = 0.10, P = not significant) or CA2-3 (r = 0.35, P = not significant) regions. Memory performance with the contralateral hemisphere was not significantly correlated with ipsilateral hippocampal densities. These data support the role of the hippocampus in human memory and show further evidence of hippocampal subfield specificity in the relationship between memory performance and neuronal cell loss. Further studies of the dentate granule and hilar regions in relation to human memory are warranted.
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PMID:Unilateral hemispheric memory and hippocampal neuronal density in temporal lobe epilepsy. 847 48

In the gerbil (Meriones unguiculatus) hippocampal formation, the calcium-binding protein parvalbumin (PV) shows a unique species-specific distribution: it is present in the perforant path from the entorhinal cortex to the stratum molecular of the dentate are and cornu ammonis. A possible relation of this to the seizure-sensitivity of gerbils has been suggested. In addition, as in other species, PV is contained in a subpopulation of GABAergic nerve cells of the gerbil hippocampus. The characteristics of these PV-containing neurons are here described. Distribution and shape of the PV-positive neurons in general agreed with the features described for rat hippocampus with two notable exceptions: in CA2 PV-containing perikarya were densely crowded and gave rise to an intense immunoreactive plexus around the pyramidal cells and, in CA1, the number of stained neurons was variable, often much lower than in rats and occasionally not a single PV-positive neuron was present. In parasagittal brain sections of the lateralities 1.0, 1.6 and 2.2 mm from the midline, obtained from 27 male gerbils, the number of PV-containing neurons was determined. The data set obtained in CA3 and dentate area resembled unimodal distributions, while in CA1 a bimodal frequency distribution was present. Since parametric and non-parametric correlation tests rely on a unimodal distribution of the data set, they gave falsely significant values in CA1. The bimodal distribution suggests that, with respect to the PV-containing interneurons in CA1, two different populations of gerbils were included in our sample, those with many positive neurons and those with only a few. Since the nerve terminal staining is preserved also in those gerbils with only a few positive perikarya in CA1, it seems possible that an unknown factor influenced PV expression and storage in the soma. Sex, age, seasonal or circadian rhythm or quality of immunocytochemical staining did not influence the outcome of the quantitative analysis. However, a relation of the expression of the high affinity calcium buffering PV in interneurons and the individual seizure sensitivity of the gerbil is considered.
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PMID:Distribution of parvalbumin-containing interneurons in the hippocampus of the gerbil--a qualitative and quantitative statistical analysis. 856 51

Severe, repetitive ("binge") ethanol intoxication in adult rats (intragastric delivery 3 times daily for 4 days in a modification of the Majchrowicz method) precipitates neuronal degeneration in selected cerebral cortical regions involved in memory and olfaction, confirming the results of Switzer and colleagues (Anat. Rec. 202: 186a, 1982). Neuronal damage was visualized with the de Olmos cupric silver technique for degenerating neurons and processes (argyrophilia), and was quantitated by total counts and densities of argyrophilic cells/fields. The specificity of the degeneration provides a neuropathological basis for the olfactory memory deficits in chronic alcoholics. In highly intoxicated rats, argyrophilia was most extensive among hippocampal dentate gyrus granule cells, pyramidal neurons in layer 3 of the entorhinal cortex, and olfactory nerve terminals in the olfactory bulb. Degenerating pyramidal neurons were also consistently seen in the insular cortex and olfactory cortical regions, such as the piriform and perirhinal cortices. There were few argyrophilic neurons in the CA regions of the hippocampus and none in the cerebellum--regions generally shown to have cell loss in long-term ethanol feeding models--but degenerating mossy fibers in the CA2 region were observed. Degeneration was maximal before the peak period of abstinence symptoms in this model, because argyrophilic densities were no greater 36 hr, compared with 8 hr after the last ethanol dose. High blood ethanol levels were required, because argyrophilia, absent from isocaloric controls, also was only evident in ethanol-intoxicated rats with mean blood ethanol levels for days 2 to 4 above 300 mg/dl; however, it increased substantially between 350 and 550 mg/dl. The resemblance of the argyrophilic distribution to the regional neuropathology that occurs in experimental seizures indicates that the ethanol-induced degeneration may have an excitotoxic basis. Progressive reductions in the seizure threshold (e.g., kindling phenomena that have been documented during binge ethanol intoxication) might be associated with excitotoxic hyperactivity during the repetitive nadirs between high blood and brain ethanol peaks. However, direct toxic actions of ethanol or its metabolites could also be involved. Overall, the model should be useful for studying mechanisms of ethanol-induced selective cortical and olfactory brain damage.
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PMID:Neuronal degeneration in rat cerebrocortical and olfactory regions during subchronic "binge" intoxication with ethanol: possible explanation for olfactory deficits in alcoholics. 873 Feb 19

Methylazoxymethanol acetate (MAMac) is a potent teratogenic agent which can produce ectopic cell placement in developing rat brains. In the present study, we evaluated (i) whether prenatal exposure to MAMac results in a lowered seizure threshold to flurothyl and (ii) if there is a correlation between the number of ectopic cells in MAMac-exposed hippocampus and flurothyl-induced seizure latency. In 60 day old (P60) rats exposed to MAMac in utero, the latencies to myoclonic jerk (173 +/- 2.3 s) and forelimb clonus (215 +/- 4.6 s) were significantly shorter than those of controls (200 +/- 6.9 s and 238 +/- 8.8 s, respectively). MAMac also increased the proportion of flurothyl-treated rats that progressed from bilateral forelimb clonus to generalized tonic-clonic seizures (control: 33%; MAMac: 91%). Shorter seizure latencies were associated with an increased number of ectopic pyramidal cells in region CA1/CA2. These results suggest seizure susceptibility is enhanced in an animal model (MAMac) characterized by abnormal neuronal migration.
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PMID:Flurothyl seizure susceptibility in rats following prenatal methylazoxymethanol treatment. 873 22

Localized injections of 50 microM tetrodotoxin (TTX) in rat hippocampal slices blocked stimulus train-evoked electrographic seizures (EGSs) for several hours. Responses to single stimuli were minimally altered during TTX block of the EGSs. This selective reduction of epileptiform activity could result from general blockade of action potentials in an anatomically distinct group of neurons in the slice. To test this hypothesis, we systematically mapped TTX injection sites in the hippocampal slice, and found that TTX injections that blocked EGSs were nearly always located in or invaded CA2/3 stratum radiatum and/or stratum lacunosum-moleculare. A high degree of recurrent activity in this region contributes to both epileptiform activity and responses to single stimuli; hence our selective inhibition of EGSs suggests a more pharmacologically specific anticonvulsant effect of TTX. Consistent with this hypothesis, we found that low concentrations of TTX (5, 10, or 20 nM) in the perfusion medium blocked EGSs without decreasing the amplitude of extracellular responses to single stimuli. Polysynaptic activity and/or antidromic firing may be particularly vulnerable to TTX action on voltage-gated sodium channels, due to their lower the safety factor for action potential propagation. Selective reduction of this activity may disrupt the abnormal neuronal activity underlying EGSs.
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PMID:Selective suppression of in vitro electrographic seizures by low-dose tetrodotoxin: a novel anticonvulsant effect. 877 98


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