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

This study concerns expression of the genes encoding three multifunctional proteins: clusterin and two complement cascade components, C1q and C4. Previous work from this and other laboratories has established that clusterin, Clq and C4 messenger RNAs are elevated during Alzheimer's disease, and in response to deafferenting and excitotoxic brain lesion. This study addresses hippocampal clusterin, ClqB and C4 expression in response to neurotoxins that caused selective neuron death. Kainate, which preferentially kills hippocampal CA3 pyramidal neurons but not dentate gyrus granule neurons induced clusterin immunoreactivity in CA1 and CA3 pyramidal neurons and adjacent astrocytes, but not in dentate gyrus granule neurons. In contrast, colchicine, which preferentially kills the dentate gyrus granule neurons, induced clusterin immunoreactivity in the local neuropil as punctate deposits, but not in the surviving or degenerating dentate gyrus granule neurons. Clusterin messenger RNA was increased in astrocytes. ClqB and C4 messenger RNAs increased within 48 h after kainate injections, particularly in the CA3 pyramidal layer, less in the dentate gyrus-CA4, and less in CA1. Clq immunoreactivity was detected in CA1 pyramidal neurons and also as small punctate deposits in the CA1 region at eight and 14 days after kainate. The increase of both clusterin and ClqB messenger RNAs after kainate injections was blocked by barbiturates that prevented seizures and neurodegeneration. In primary hippocampal neuronal cultures treated with glutamate, a subpopulation of cultured neurons that survived glutamate toxicity also had parallel elevations of clusterin and ClqB messenger RNA. In conclusion, cytotoxins that target selective hippocampal neurons increase the expression of both clusterin and ClqB in vivo and in vitro. These results show that elevations of clusterin messenger RNA or protein can be dissociated from each other and from cell death. These increased messenger RNAs were associated with immunoreactive deposits that differed by cell type and intra- versus extracellular locations. These results suggest that the complement system is involved in brain responses to injury.
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PMID:Selective expression of clusterin (SGP-2) and complement C1qB and C4 during responses to neurotoxins in vivo and in vitro. 787 Mar 3

Invasive EEG recording of spontaneous seizures and correlations of findings with histopathology have defined a characteristic set of electrographic findings in medial temporal lobe epilepsy. The presence of periodic spikes before seizure onset has a significant correlation with reduced CA1 cell counts. This phenomenon is followed, in spontaneous seizures, by 13-25 Hz discharge in medial temporal lobe structures. Temporal neocortical seizure onsets have significantly faster frequencies than hippocampal onsets; hippocampal ictal onset frequencies also vary more often than neocortical onsets. Although hippocampus or entorhinal cortex are involved to a variable degree, the periodic spikes are more consistently seen in hippocampus. Sixty percent of mesial temporal ictal onsets initially propagate to the ipsilateral temporal neocortex. In another 30%, the initial area of propagation is the contralateral hippocampus, to which propagation occurs before involvement of the ipsilateral or contralateral temporal neocortex. Time to propagation of the seizure to the contralateral hippocampus is lengthened in direct proportion to CA4 cell loss, suggesting a role for CA4 in this process. Long interhemispheric propagation times are associated with good surgical outcomes and with the presence of mesial temporal sclerosis. This article also discusses correlation with hippocampal slice physiology, and significance of these findings in understanding the pathophysiology of medial temporal lobe epilepsy.
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PMID:Invasive electroencephalography in mesial temporal lobe epilepsy. 789 8

The behavioural, electrocortical (ECoG) and neurodegenerative effects of intrahippocampal injection of paraquat, a well-known free radical producing agent, were studied in rats. Injection of paraquat (100 nmol) into one dorsal hippocampus produced limbic motor and ECoG seizures. These effects were accompanied at 24 h by severe damage to CA1, CA3 and CA4 hippocampal pyramidal neurones and dentate gyrus granule cells. In comparison to the cell number counted in control, untreated, side of the hippocampus, significant (P < 0.05) neuronal loss was observed in the CA1 and CA3 pyramidal cell layers of the treated hippocampus. A lower dose of the herbicide (10 nmol) did not produce consistent motor and ECoG effects and in no instance was significant neuronal loss observed. A pretreatment with U74389F [21-4-(2,6-di-l-pyrrodinyl-4-pyridinyl)-1-piperazinyl-pregna-1,4,9 (11)triene-3,20-dione monomethansulfonate] (30 mg/kg i.p., 15 min before paraquat) completely protected rats from motor and ECoG epileptogenic effects induced by intrahippocampal paraquat (100 nmol). This dose of U74389F also reduced the hippocampal damage typically produced by paraquat and no significant neuronal loss was reported in the CA1 and CA3 pyramidal cell layers. A lower dose of U74389F (10 mg/kg i.p.) did not afford any protection against the epileptogenic effects produced by paraquat (100 nmol); in these animals hippocampal damage was still evident though neuronal loss did not reach statistical significance. In conclusion, the present data show that systemic administration of U74389F possesses neuroprotective effects against seizures and neurodegeneration typically elicited by intrahippocampal injection of paraquat.
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PMID:Neurodegeneration produced by intrahippocampal injection of paraquat is reduced by systemic administration of the 21-aminosteroid U74389F in rats. 792 Nov 67

The changes of opioid peptide reactivity in seizure activity have been well studied in animals. Increased enkephalin and dynorphin immunoreactivity in the hippocampi of animals are interpreted as the result of seizure induced mossy fibre sprouting. We studied the hippocampi of six patients with a history of long-standing grand mal seizures and six age-matched control patients with no history of epilepsy or neurologic disease, using frozen sections which were immunostained with antibodies against Leu-enkephalin and Met-enkephalin. The staining intensity in the CA3, CA4 and internal molecular layer of the dentate fascia in each case was quantified using optical densitometry image analysis. The CA3 and CA4 of the epileptic hippocampi showed highly significant increase in Leu-enkephalin-like immunoreactivity compared to the controls (P < 0.005) while the inner molecular layer showed only significant increase (P < 0.05). Met-Enkephalin-like immunoreactivity was only significantly increased in CA4 of the epileptic hippocampi (P < 0.05).
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PMID:Increase in enkephalin-like immunoreactivity in hippocampi of adults with generalized epilepsy. 795 7

Surgically resected hippocampi from children with extrahippocampal seizures and structurally non-atrophic brains were examined to determine the relationship of neuron losses and aberrant mossy fiber (MF) sprouting to the postnatal migration and differentiation of the fascia dentata (FD) granule cells (GC). Percent neuron loss compared to age-matched autopsy controls was determined by quantitative cell densities, and aberrant MF sprouting by neo-Timm histochemistry. Postnatal immature GC migration and differentiation was demonstrated by the transient but GC-specific expression of the immature form of neural cell adhesion molecule (NCAM-H). Results showed that the hippocampi from children with seizures appeared microanatomically intact without focal areas of damage. However, significant neuron losses were found by neuron counts in the fascia dentata (P < 0.01), CA4 (P < 0.01), and CA2 (P < 0.05). Aberrant supragranular inner molecular layer MF sprouting was found in hippocampi of children with seizures, and the MFs showed smaller puncta in specimens resected under 2 years of age (n = 3) compared to the larger puncta in older children (n = 5). Hippocampi from children under 2 years of age also demonstrated NCAM-H positive primitive cells in the infragranular and stratum granulosum of the fascia dentata consistent with the postnatal migration and differentiation of GCs, the parent neurons of the MFs. These results indicate that seizures in the immature but structurally intact human hippocampus are associated with decreased neuron densities and aberrant MF sprouting very early in postnatal development. The data also show that aberrant MF sprouting is found during postnatal migration, differentiation and axogenesis of GCs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Children with severe epilepsy: evidence of hippocampal neuron losses and aberrant mossy fiber sprouting during postnatal granule cell migration and differentiation. 800 75

To clarify experimentally whether benzodiazepine (Bz) receptor or regional cerebral blood flow (rCBF) imaging is more sensitive in the detection of epileptic foci, we simultaneously examined the Bz receptor and rCBF distribution changes in hippocampal kindled rabbits with in vivo double tracer autoradiography using 125I-labeled Ro 16-0154 (125I-Iomazenil) and 99mTc-labeled hexamethylpropylene amine oxime (99mTc-HMPAO). In visual and quantitative analyses, 125I-Iomazenil accumulation in brain slices extracted after the completion of the kindling was markedly and extensively decreased in the kindled right CA1 region, and further in the right temporal lobe, dentate gyrus, CA2, CA4, and bilateral CA3 regions, regarded as the propagated sites of seizure discharges. 99mTc-HMPAO accumulation was much more slightly and less extensively decreased in the right CA1, frontal, temporal and dentate gyri. Further, this decrease in 125I-Iomazenil accumulation was not due to neuropathological abnormalities, which consisted only of tissue damage corresponding to electrode track in the CA1. Both the kindled and propagated sites are known to have a possibility of acquiring epileptogenesis as experimental epileptic foci. These results suggest that Bz receptor imaging is much more sensitive in the detection of epileptic foci than rCBF imaging, and therefore that Bz receptor imaging is useful in clinical epilepsy.
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PMID:Comparison of benzodiazepine receptor and regional cerebral blood flow imaging of epileptiform foci in hippocampal kindled rabbits: a study with in vivo double tracer autoradiography using 125I-iomazenil and 99mTc-HMPAO. 803 93

Glial cell line-derived neurotrophic factor (GDNF) is a novel member of the transforming growth factor-beta superfamily with potent trophic effects on dopamine neurons. Kainate-induced epileptic seizures have been shown to induce gene expression of trophic factors, particularly members of neurotrophin or fibroblast growth factor families, in the hippocampus. In this study, we examined the effects of kainate (12 mg/kg, i.p.)-induced epileptic seizures on the expression of the novel neurotrophic factor GDNF in the hippocampus. While GDNF messenger RNA was not detected during development or in normal adult rats in the hippocampus, kainate-induced epileptic seizures markedly increased GDNF messenger RNA in scattered neurons in the dentate granule layer 3 h after injection. Six hours after kainate almost all dentate granule cells and expressed GDNF messenger RNA. The increase in GDNF messenger RNA in the dentate granule layer returned almost to control levels 24 h after kainate; however, there was still expression of GDNF messenger RNA in the hilus/CA4 and also in pyramidal neurons in areas CA1-CA3. We conclude that GDNF messenger RNA is regulated, in part, via glutamate-mediated excitation and may play a role in long-lasting structural and/or functional reorganization in the hippocampal formation.
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PMID:Neurons of the hippocampal formation express glial cell line-derived neurotrophic factor messenger RNA in response to kainate-induced excitation. 805 21

The neuroprotective effect of a novel anticonvulsant, zonisamide, was investigated in neonatal rats with hypoxic-ischemic brain damage. Rats underwent left carotid ligation followed by hypoxic exposure (8% O2) for 2.5 h. When zonisamide (75 mg/kg) was administered i.p. 1 h before hypoxia, it reduced the cortical infarction volume to 6 +/- 5% (mean +/- S.E.M.) from 68 +/- 7% in vehicle-treated controls and the striatal volume to 8 +/- 4% from 78 +/- 7%. Zonisamide also reduced neuronal necrosis in 5 hippocampal regions (the dentate gyrus, CA4, CA3, CA1, and the subiculum). The plasma zonisamide concentration before and after hypoxia was 47.9 +/- 2.0 microgram/ml and 42.3 +/- 3.9 microgram/ml, respectively. Epidural electrodes were implanted in 6 pups one day before hypoxia-ischemia. Electroencephalograms were recorded during hypoxia-ischemia in rats given zonisamide or vehicle before the insult. The intensity of seizure activities was similar in the zonisamide-treated pups and the vehicle-treated controls. These findings demonstrate that zonisamide reduces neonatal hypoxic-ischemic brain damage and that this protective effect does not depend on its anticonvulsant action.
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PMID:Zonisamide reduces hypoxic-ischemic brain damage in neonatal rats irrespective of its anticonvulsive effect. 808 94

Domoic acid (0.6 mg/kg) was injected intravenously through the caudal vein in pregnant female mice on the 13th day of gestation and EEG was monitored in the developing progeny during postnatal days 10-30. No clinical seizure activity was observed during this period. However, these mice demonstrated generalized electrocortical inhibition associated with diffuse spike and wave activity in their basal EEG records. Intrauterine domoic acid-exposed (IUD) mice had significantly reduced seizure thresholds to an additional dose of domoic acid, given postnatally. At the light microscopic level, hippocampus of IUD mice exhibited age related developmental neurotoxicity. No cellular damage was observed on postnatal day 1. On day 14, severe neuronal damage was observed in the hippocampal CA3 and dentate gyrus regions. On day 30, in addition to CA3 and dentate gyrus, CA4 was also involved. Brain regional GABA levels were significantly reduced and glutamate levels increased in IUD mice. Kainate receptor binding to hippocampal synaptosomal membranes from IUD mice at 30 d of age was significantly increased. There was also an enhanced 45Ca influx into cortical and hippocampal slices of these mice. These findings suggest that intrauterine exposure to domoic acid can induce hippocampal excitotoxicity by increasing the neuronal calcium influx through kainate receptor activation. Histological changes suggest progressive hippocampal damage in IUD mice, but without overt clinical seizures.
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PMID:Hippocampal changes in developing postnatal mice following intrauterine exposure to domoic acid. 810 41

The epileptogenic and neurodegenerative effects induced by intra-hippocampal injection of a selective K+ channel inhibitor, alpha-dendrotoxin (DTx), were investigated in normal rats and those bearing a monolateral surgical lesion of the Schaffer collaterals that causes degeneration of their nerve terminals and also, isolates the CA3 area. In addition, these effects have also been studied in rats pretreated with NBQX, an AMPA receptor antagonist. Injection of DTx (35 pmol) into one dorsal hippocampus induced motor and electrocortical (ECoG) seizures in all the treated animals that were rapid in onset (within 2-3 min). The seizures were accompanied at 24 h by significant neuronal cell loss which occurred in the CA1, CA3 and CA4 pyramidal cell layers of the hippocampus, ipsilateral to the side of injection. This neuronal loss was paralleled by a significant decrease in the density of radioiodinated DTx labelled acceptors. Lesioning of the excitatory afferents to the CA1 pyramidal cells, gave a substantial reduction in the density of radioiodinated DTx labelled acceptors in the strata oriens and radiatum, revealing that a proportion of these K+ channels are present on the Schaffer collateral terminals. Under these conditions, motor and ECoG seizures persisted. As expected, the lesion prevented loss of the isolated CA3 pyramids, normally produced by the administration of DTx, leaving unaffected CA1 and CA4 pyramidal cell damage, consistent with an observed diminution of DTx binding sites in the latter areas. In unlesioned rats pre-treated with NBQX (30 mg/kg i.p.), subsequent injection of DTx evoked epileptogenic effects after a latency of 15 min and caused significant cell loss in the CA1 but not in the CA3 and CA4 pyramidal cell layers, ipsilateral to the side of toxin injection. A lower dose of NBQX (15 mg/kg i.p.) proved ineffective. In conclusion, these data together with our published results on NMDA antagonists indicate that motor and ECoG seizures and CA1 pyramidal cell loss elicited by intra-hippocampal injection of the K+ channel blocker, DTx, are independent from mechanisms involving glutamate-mediated excitotoxicity whereas CA3 and CA4 pyramidal cell loss may be the consequence of excessive activation of AMPA receptors.
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PMID:Hippocampal damage produced in rats by alpha-dendrotoxin--a selective K+ channel blocker--involves non-NMDA receptor activation. 813 Jul 39


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