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)

Unilateral lesions of the entorhinal cortex have been shown to lead to dramatic increases in GFAP mRNA levels in denervated zones in the hippocampus and dentate gyrus and sometimes (but not always) in nondenervated zones in the contralateral hippocampus and dentate gyrus. The variable distribution of the increases in GFAP mRNA expression suggests that the events which trigger changes in GFAP mRNA levels occur to a variable extent in individual animals. The companion paper characterizes two candidate triggering events: spreading depression (SD) that occurs to a variable extent at the time of the lesion and recurrent seizures that occur during the early postlesion interval. The goal of the present study was to evaluate whether individual differences in the extent or spatial distribution of lesion-induced increases in GFAP mRNA are related to the occurrence of either SD or seizures. We quantified the increases in GFAP mRNA levels in individual animals that had been monitored physiologically to define the incidence of SD and postlesion seizures. The results revealed that the quantitative extent of the increases in GFAP mRNA in denervated zones and was not related to either SD or postlesion seizures. The increases in GFAP mRNA in nondenervated zones also were not related to episodes of spreading depression that occurred at the time of lesion production but were related to the spontaneous seizures that developed during the first 24 h postlesion after the animals had recovered from the surgical anesthesia. Taken together, these data indicate that physiological events that occur during the early postlesion interval can play an important role in determining the pattern and extent of altered cellular gene expression in response to an injury.
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PMID:The role of postlesion seizures and spreading depression in the upregulation of glial fibrillary acidic protein mRNA after entorhinal cortex lesions. 863 71

Reactive gliosis is a response of astrocytes to a variety of insults that is characterized by hypertrophy of the cell bodies and processes and an increase in the expression of glial fibrillary acidic protein (GFAP). The signal that regulates the transition to the reactive state and the role of vimentin in reactive gliosis are unknown. The experiments here used a model of repeated seizures in the hippocampal-parahippocampal circuits to determine the extent and time course of reactive gliosis, including the appearance of vimentin, in response to seizures. Reactive gliosis, detected by immunohistochemistry for the presence of GFAP and vimentin, was present 2-7 days after the repeated seizures. At least 9 seizures, or at least 250 s of seizure discharge, were needed to induce reactive gliosis. After seizures, cells staining for vimentin were found in the dentate gyrus molecular layer and hilar region, as well as in the molecular layer of CA1. Fewer cells were stained in the CA3 region. These experiments demonstrate that repeated discrete seizures of the hippocampal-parahippocampal circuits can cause reactive gliosis and localized induction of a glial protein (vimentin) that is not normally expressed in the adult brain.
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PMID:Repeated seizures increase GFAP and vimentin in the hippocampus. 873 64

Kainic acid-induced limbic seizures enhance expression of tenascin-C (TN) in the hippocampus of adult rats. TN mRNA was detectable by in situ hybridization in many granule cells in the dentate gyrus 4.5 hr after kainic acid injection but not in saline-injected animals (controls) or in animals killed 2 or 24 hr after injection. Thirty days after kainic acid injection, TN mRNA was detectable only in pyramidal cells of CA3 and CA1. At the protein level, TN was detectable by immunocytochemistry in control animals in the strata oriens and lacunosum moleculare of CA1, in the molecular layer, and within a narrow area at the inner surface of the granule cell layer in the dentate gyrus. Twenty-four hours after kainic acid injection, TN immunoreactivity was enhanced in these areas and throughout the granule cell layer. Thirty days after kainic acid injection, TN immunoreactivity was downregulated in these areas, while it was prominent in the stratum oriens and in clusters of immunoreactivity in the stratum lucidum of CA3. Western blot analysis of the hippocampus showed a peak of TN expression 24 hr after kainic acid injection. These observations show that TN expression is upregulated in predominantly neuronal cells already by 4.5 hr after kainic acid injection, coincident with activation of granule cells and sprouting of axon terminals, whereas the remaining TN expression 30 days after injection relates to pyramidal cells in CA1 and CA3, coincident with an astroglial response, as marked by a strong expression of glial fibrillary acidic protein.
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PMID:Kainic acid activates transient expression of tenascin-C in the adult rat hippocampus. 873 55

Immunocytochemical methods were used to study alterations in inhibitory neuronal circuits in human neocortex resected during surgical treatment of intractable temporal epilepsy associated or not with brain tumours. The epileptogenic cortex was characterized and divided into spiking or non-spiking zones by intraoperative electrocorticography (ECOG). The resected cortex was cut into blocks, sectioned and stained immunocytochemically for visualization of glutamic acid decarboxylase (GAD), the calcium-binding protein, parvalbumin (PV) and glial fibrillary acidic protein (GFAP). A variety of alterations in cortical neuronal circuits as revealed by immunocytochemical and histological methods were found. Similar alterations in inhibitory neuronal circuits appear to occur independently of the primary epileptogenic site and pathology associated with epilepsy, which suggests that there is possibly a common basic underlying mechanism that leads to seizure activity. These changes were apparently unrelated to ECOG findings at surgery, which bring into question the value of the use of interictal epileptic discharges recorded by ECOG to guide cortical resections. The most conspicuous and common change was the loss of chandelier cells. The finding that these cells are among the most vulnerable types of GABAergic interneurons in the epileptogenic temporal cortex indicates that they might be of great functional importance, since the axon terminals of chandelier cells are likely to exert powerful regulation of impulse generation in cortical pyramidal cells. Therefore, these cells might represent a key component in the aetiology of human epilepsy.
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PMID:Inhibitory neurons in the human epileptogenic temporal neocortex. An immunocytochemical study. 881 95

Protein F1/GAP-43 is differentially expressed in brain with high levels present in regions associated with memory functions. However, in hippocampus the granule cells lack F1/GAP-43 expression. To determine if this lack of expression is due to inhibitory signals from the target cells, we selectively destroyed CA3 pyramidal cells unilaterally using microinjections of excitotoxins. Kainate lesions induced F1/GAP-43 mRNA expression bilaterally in granule cells at 24 h post-injection. Since the induction contralateral to the lesion was not due to loss of target cells, that induction may be ascribed to consequences of seizure activity. However, F1/GAP-43 mRNA hybridization decreased by 3 d post-lesion and was at background levels by 6 d, indicating that the lack of F1/GAP-43 expression in granule cells is restored despite a lack of target neurons. Unilateral lesions of CA3 cells using ibotenate, which are not as complete as kainate but do not cause seizures, did not induce F1/GAP-43 mRNA in granule cells on either the contralateral or, in 4 of 5 cases, the ipsilateral side. Taken together, these data suggest that the CA3 target is not essential for the absence of F1/GAP-43 expression in granule cells. To compare the extent of damage caused by the lesions, we investigated the location of astrocytes undergoing reactive gliosis, employing as a reporter glial fibrillary acidic protein (GFAP) gene expression. After both kainate and ibotenate injections GFAP hybridization increased in the lesioned area as well as in the contralateral hippocampus. These results indicate that injections of kainate, and possibly ibotenate to a lesser extent, may affect behavior not only by damaging cells at the injection site, but also by altering gene expression in cells at distant sites.
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PMID:Is the lack of protein F1/GAP-43 mRNA in granule cells target-dependent? 882 59

The time course of induction of the proto-oncogene c-fos and the inducible heat shock hsp70 gene was studied from 5 minutes to 24 hours at both transcriptional (c-fos and hsp70 mRNA) and translational levels (C-FOS and HSP72 proteins) in the rat hippocampus and piriform cortex (Pir) after soman-induced seizures. Induction of c-fos was noticed as early as 5 minutes after seizures onset in all fields of hippocampal formation (CA1, CA3, CA4, and dentate gyrus) and in piriform cortex. The most intense induction was observed in piriform cortex. A sustained activation of c-fos occurred in Pir and in CA1, CA3, and CA4 areas of hippocampus. Nevertheless, histological analysis showed rare affected neurons in CA4, whereas damage was severe in Pir and in CA1 and CA3 hippocampal subfields. Induction of hsp70 mRNA occurred but was delayed in all areas previously exhibiting c-fos expression. Nevertheless HSP72 protein was never expressed in the structures where injury was high (i.e., CA1 and piriform cortex) and mainly occurred in the less damaged structure (i.e., CA4 area of hippocampus). Regional expression of glial fibrillary acidic protein mRNA was also studied in order to exclude an astroglial origin of the c-fos and hsp70 gene inductions. Our results demonstrated that after soman induced-seizures 1) there was no strict correlation between time course or intensity of neuronal c-fos induction and subsequent neuropathology, and 2) the most lesioned areas did not express HSP72 protein in spite of intense mRNA induction, suggesting that transcriptional and translational events for hsp70 gene might vary according to the severity of seizure insult.
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PMID:Time course and regional expression of C-FOS and HSP70 in hippocampus and piriform cortex following soman-induced seizures. 887 16

The molecular mechanisms that underlie dentate granule cell axon (i.e., mossy fiber) growth during development and following seizure-induced hippocampal injury remain unknown. Part of this process may involve specific factors that support dentate granule cells during differentiation, and molecular cues that allow the appropriate growth of mossy fiber axons toward their targets. To study this process, we developed an in vitro assay system to measure the activity of putative trophic, chemoattractant and chemorepulsive factors. Two-hundred-micrometer-thick transverse hippocampal sections were prepared from neonatal rats and microdissected to isolate the middle one-third of the superior blade of the dentate granule cell layer. These were embedded in a three-dimensional collagen matrix either alone or with microdissected regions of the CA2 pyramidal cell layer. Cultures were maintained in a defined medium and grown for two to three days in a standard culture environment. Results showed that numerous processes grew primarily from the hilar side of explants into the collagen matrix, often in excess of 500 microns in length. These were determined to be axons based on: (i) morphological criteria including size and presence of growth cones, (ii) synaptophysin and growth-associated protein-43 immunoreactivity, (iii) lack of glial fibrillary acidic protein immunoreactivity and (iv) contiguity of biocytin-filled processes with neuronal soma within the explant. Treatment of cultures with brain-derived neurotrophic factor caused a significant increase in axon number and length, and this effect was partially reversed by the addition of a trkB-immunoglobulin fusion protein that blocks the activity of brain-derived neurotrophic factor and neurotrophin-4/5. Basic fibroblast growth factor also caused a marked increase in axon number and length, and caused a migration of neuron-like cells out of the explant into the collagen. These results show that cultured dentate granule cell layer explants are capable of growing mossy fibers into a neutral collagen matrix, and the growth of axons can be modified by the addition of exogenous growth factors. Furthermore, since target tissue and point sources of purified factors can easily be co-cultured with the explants, this new system provides a direct means for testing the molecular cues that influence mossy fiber growth.
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PMID:Dentate granule cell layer collagen explant cultures: spontaneous axonal growth and induction by brain-derived neurotrophic factor or basic fibroblast growth factor. 889 86

Increased gene expression for two species of cytosolic fatty acid binding proteins (FABPs) after systemic administration of kainic acid in the rat brain was demonstrated by Northern blotting and in situ hybridization histochemical analyses. The expression of brain (B)- and skin (S)- but not heart (H)-FABP mRNAs were markedly elevated in the hippocampus at 48 h after systemic kainate treatment. The elevated expression patterns of B- and S-FABP mRNAs were quite similar to that for glial fibrillary acidic protein in the normal brain, suggesting strongly that the increased expression for B- and S-FABPs occurs in dedifferentiated and proliferated astrocytes in response to kainic acid-induced seizure.
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PMID:Increased expression of the mRNA for brain- and skin-type but not heart-type fatty acid binding proteins following kainic acid systemic administration in the hippocampal glia of adult rats. 891 95

The levels of glial fibrillary acidic protein mRNA were analysed by in situ hybridization during the first 6 h in experimental models of status epilepticus in the rat. Two different models of status epilepticus were studied: one is produced by the administration of pilocarpine to lithium-treated rats and the other by the intracerebroventricular administration of kainate. Results obtained in the present study showed a very rapid (as early as 1.5 h in periventricular zones of hypothalamus, cerebral cortex, and hippocampal area) up-regulation of GFAP mRNA levels following the pharmacological induction of seizures. Several other areas showed a GFAP activation starting at 3 h such as septum, habenular nuclei, corpus callosum, and cingulum. The comparison of the results obtained in the two models of status epilepticus revealed interesting differences in some brain areas, such as cerebellum and striatum, which can be related to the specific neurotransmitter receptors and neurochemical pathways stimulated by the drugs. Interestingly, some brain areas whose neurons are strongly activated by pilocarpine and kainate (amygdala and CA3 hippocampal field) and that undergo neuronal degeneration did not show the early GFAP response. An interesting spatial feature was observed in several brain regions examined (striatum, septum, and hypothalamus): the response first appeared in the periventricular zones and then diffused to the rest of the brain area. In general GFAP responses in the periventricular zones were early and intense.
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PMID:Induction of astroglial gene expression by experimental seizures in the rat: spatio-temporal patterns of the early stages. 892 4

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


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