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

Is the heat shock response physiologically relevant? For example, following hyperthermia or ischemia, what neural cell types show induction of heat shock genes and what is the time course of the effect? Initial experiments in this area demonstrated the prominent induction of a 70 kDa heat shock protein (hsp70) when labeled brain proteins isolated from hyperthermic animals were analyzed. Recently, in situ hybridization and immunocytochemistry have been utilized to map out the pattern of expression of both constitutively expressed and stress-inducible members of the hsp70 multigene family. Different types of neural trauma have been found to induce characteristic cellular responses in the mammalian brain with regard to the type of brain cell that responds by inducing hsp70 and the timing of the induction response. Fever-like temperature causes a dramatic induction of hsp70 mRNA within 1 hr in fiber tracts of the forebrain and cerebellum, a pattern consistent with a strong glial response to heat shock. Tissue injury, namely, a small surgical cut in the cerebral cortex, induces a rapid and highly localized induction of hsp70 mRNA in cells proximal to the injury site. Using an immunocytochemical approach, a neuronal pattern of induction of hsp70 has been demonstrated following ischemia or kainic acid-induced seizures. It is apparent that the pattern of induction of hsp70 may be a useful early marker of cellular injury and may identify previously unrecognized areas of vulnerability in the nervous system.
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PMID:Induction of heat shock (stress) genes in the mammalian brain by hyperthermia and other traumatic events: a current perspective. 209 76

Induction of messenger RNA encoding the 70-kDa heat shock or stress protein, hsp70, and the product of the proto-oncogene c-fos was evaluated in gerbil hippocampus by in situ hybridization at various recirculation intervals after 5 minutes of ischemia. Striking increases in c-fos RNA were observed in dentate granule cells within 15 minutes of recirculation and remained evident through 1 hour, returning to undetectable control levels by 3 hours. Modest c-fos hybridization was seen in CA1 and CA3 neurons during the same time course. These results are consistent with the rapid and transient stimulation-induced c-fos expression observed in many experimental systems. Hsp70 expression showed a longer time course, being strongly induced in all major hippocampal neuron populations within 3 hours and persisting for approximately 12 hours in dentate granule cells and through 24 hours in CA3 pyramidal neurons. Notably, the most prolonged expression of hsp70 RNA was observed in vulnerable CA1 neurons that minimally accumulate the immunoreactive protein, with hybridization detected essentially until the death of this cell population at 3-4 days. These studies demonstrate an overlapping distribution of hsp70 and c-fos expression in gerbil hippocampus after ischemia, although there are differences in time course and in the relative induction observed in different neuron populations. The transient increase in c-fos hybridization in dentate granule cells is identical to that seen in various seizure paradigms and provides further support for activation of hippocampal circuitry after ischemia. The prolonged time course of hsp70 messenger RNA expression in vulnerable CA1 neurons may provide a molecular correlate of proposed excitotoxic mechanisms mediating delayed neuronal death.
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PMID:70-kDa heat shock protein and c-fos gene expression after transient ischemia. 212 54

The c-fos immediate early gene is induced by normal stimuli including light, stress, hyperosmolar solutions, and hormones. Ischemia, hypoxia, seizures, cortical injury, nerve section and other pathological stimuli can also induce c-fos. The induction can occur via increases in intracellular calcium that act through a Ca2+/cAMP element on its promoter, or via trophic and other factors that act through a serum response element (SRE) on its promoter. Several studies show that calcium entry via voltage sensitive calcium channels (VSCCs) is important for inducing c-fos. We have shown that calcium entry via the NMDA receptor is important for induction of c-fos mRNA by glutamate and cAMP in cultured cortical neurons. Moreover, the NMDA receptor appears to regulate translation of c-fos mRNA to Fos protein when cells are stimulated with other types of stimuli including vasoactive intestinal peptide, zinc, and fibroblast growth factor. These results suggest that toxins that elevate intracellular calcium will likely induce the c-fos gene in brain. The heat shock or stress genes are induced by a wide variety of stimuli including heavy metals, heat, oxidative and ischemic stress, prolonged seizures, hypoglycemia, calcium ionophores, and certain toxins. It is believed that denatured proteins stimulate heat shock factors to bind to heat shock elements on the promoters of all heat shock genes to induce gene transcription. We and others have shown that global and focal ischemia induce the hsp70 heat shock gene in brain. Mild ischemia induces hsp70 mRNA and HSP70 protein in neurons only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in gene expression as an index of neuronal injury: heat shock and the immediate early gene response. 809 Mar 62

The hsp70 gene is induced by denatured protein in injured cells and is an extremely sensitive and reliable marker of cells injured by ischemia, seizures, and toxins. Normal brains have little detectable hsp70 mRNA or HSP70 protein. After status epilepticus produced by systemic injections of kainic acid, however, HSP70 protein is induced in neurons but not glia in brain regions known to be injured by kainic acid. Global and focal ischemia also induce the hsp70 gene in brain. The induction of HSP70 protein in hippocampus following increasing durations of global ischemia correlates with the regional and cellular vulnerability to ischemia: CA1 neurons express HSP70 after the briefest periods of ischemia followed by CA4, CA3, dentate granule neurons, glia, and lastly, endothelial cells. Moreover, as the severity of ischemia worsens, a transcriptional and/or translational blockade of the hsp70 gene occurs in the same order so that moderate degrees of ischemia induce HSP70 in CA3 neurons and dentate granule neurons but not necrotic CA1 neurons, and severe ischemia induces HSP70 in capillary endothelial cells of hippocampus but not in any infarcted neurons or glia throughout the hippocampus. Brief periods of focal ischemia induce HSP70 primarily in neurons, suggesting that even focal ischemia can produce selective neuronal injury without infarction. In some instances, HSP70 immunoreactive astrocytes surround the HSP70 immunostained neurons. Focal ischemia that produces infarction induces HSP70 primarily in endothelial cells of cerebral blood vessels in the regions of infarction and in neurons and astrocytes on the perimeter or the penumbral area of infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HSP70 heat shock gene regulation during ischemia. 824 24

A reverse transcriptase-polymerase chain reaction (RT-PCR) product obtained from ischemic rat brain RNA was used to screen a rat ischemic forebrain cDNA library for a cDNA clone containing the entire open reading frame for the inducible hsp70. The coding sequence for the rat hsp70 cDNA demonstrated significant similarities with the human hsp70 of Hunt and Morimoto (Proc Natl Acad Sci 82:6455-6459, 1985) and the mouse hsp70 of Hunt and Calderwood (Gene 87:199-204, 1990). The rat inducible hsp70 and constitutive hsc73 sequences are distinct. There was a low level of hsp70 mRNA expression in normal rat brain as in found in other tissues. hsp70 mRNA was markedly induced in rat brain 8 hours following global ischemia and kainic acid-induced seizures. Northern blots showed a approximately 2.9kb hsp70 mRNA band from control, kainic acid, and ischemic brains. RT-PCR confirmed the presence of hsp70 mRNA in normal rat brain. Since there are at least five human and six mouse inducible hsp70 genes known, many other rat hsp70 genes probably exist that could function in different cells or organelles or be induced under different circumstances.
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PMID:cDNA cloning and expression of stress-inducible rat hsp70 in normal and injured rat brain. 827 11

Specific probes were obtained using PCR cloning from rat brain for the 78 kDa glucose regulated (grp78), inducible 72 kDa (hsp70) as well as constitutive 73 kDa (hsc73) heat shock mRNAs. Grp78 and hsc73 were expressed in normal rat brain whereas hsp70 was not. Subcutaneous injection kainic acid (10 mg/kg) produced seizures and induced all three mRNAs. The induction of grp78 and hsp70 mRNAs occurred within 2 h, peaked between 6-8 h, persisted for 48 h, and returned to control levels by 72 h. Expression of the grp78 and hsp70 mRNAs after focal ischemia progressively increased with occlusion durations from 15-120 min in the cerebral cortex. Though grp78 and hsp70 mRNAs were induced modestly in the striatum by 15 min of ischemia, longer durations of ischemia were characterized by little change in the grp78 mRNA levels and relatively lower levels of hsp70 expression. This result indicates that progressive increases in the duration of ischemia in brain, prior to infarction, may produce proportional increases in transcription of the heat shock genes. However, once the duration of ischemia is long enough to produce infarction, this severely limits the availability of ATP which blocks transcription of the heat shock genes. In conclusion, concurrent induction of the heat shock genes suggests that kainic acid seizures and focal ischemia induce several different stress responses in brain cells caused by denaturation of proteins, changes of protein synthesis, and changes of protein glycosylation.
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PMID:Induction of glucose regulated protein (grp78) and inducible heat shock protein (hsp70) mRNAs in rat brain after kainic acid seizures and focal ischemia. 828 Nov 26

Changes in gene expression in the brain in response to adverse conditions, such as ischemia or excitotoxin exposure, may be part of the injury process or represent an adaptive response which may be protective during subsequent stressful events. In this review we have considered the regulation, functions and potential relationships to the pathophysiology of ischemia of several major groups of stress-induced genes, including those of the M(r) 27,000, 32,000 (heme oxygenase), 70,000 and 90,000 heat shock protein families, the glucose-regulated proteins, glucose transporters and ubiquitin. Patterns of gene expression in several injury models, including focal and global ischemia, excitotoxin/ seizure-related injury and hyperthermia are reviewed. In vitro expression studies and the phenomenon of ischemic tolerance are also discussed. It is concluded that stress gene expression provides a useful marker of cellular injury, and that disjunction of mRNA and protein expression may be indicative of imminent death in cells which survive the initial insult. Though other stress proteins may play a role, it seems unlikely that neuronal hsp70 expression is a major contributor to ischemic tolerance.
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PMID:The stress gene response in brain. 872 84

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

Kainic acid (KA) neurotoxicity was examined in transgenic (Tg) mice overexpressing human CuZn-superoxide dismutase (SOD-1). The doses of KA required to produce seizures, the severity of the seizures, and the regions damaged were similar in SOD-1 Tg and non-transgenic wild-type mice. Intraperitoneal KA injection induced seizure-related neuronal damage in the CA3 and CA1 regions of the hippocampus and in other regions of the brain in both SOD-1 Tg and wild-type mice. These damaged neurons were labeled with the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) technique up to 72 h, although no significant difference in the number of TUNEL-positive neurons was observed between SOD-1 Tg and wild-type mice. In situ hybridization showed that c-fos, c-jun, and hsp70 genes were expressed in the hippocampus, cortex, and other regions of the brain after KA treatment. The expression of these genes was maximal 1 to 4 h following KA treatment but persisted longer in the hippocampus and other regions in SOD-1 Tg compared with wild-type mice; however, cell death in the hippocampus, assessed using cresyl violet staining, was similar in SOD-1 Tg and wild-type mice. The data show that superoxide radicals modulate both immediate early gene and heat shock gene expression after KA-induced seizures. The prolonged expression of c-fos, c-jun, and hsp70 in SOD-1 Tg compared with wild-type mice may indicate that hippocampal neurons survive longer in SOD-1 Tg than in wild-type animals; however, cell death as well as the seizure threshold, seizure severity and the pattern of regional vulnerability were not affected substantially by increased levels of SOD in the brain.
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PMID:DNA fragmentation and Prolonged expression of c-fos, c-jun, and hsp70 in kainic acid-induced neuronal cell death in transgenic mice overexpressing human CuZn-superoxide dismutase. 911 97

Previous studies have shown the successive expression of c-fos and hsp70 genes, especially in the hippocampal formation, during soman-induced seizures. In order to detect a possible link between the induction of these two genes, antisense strategies have been used. First, the ability of unilateral intrahippocampal infusion of c-fos antisense oligonucleotides to inhibit ipsilateral, seizure-related, c-FOS-like immunoreactivity, was verified. Second, induction of hsp70 mRNA was investigated using in situ hybridization. Unilateral inhibition of c-fos induction clearly reduced levels of hsp70 mRNA in the c-fos antisense-infused hippocampus relative to the non-infused contralateral side. Infusion of c-fos sense probe or vehicle did not affect bsp70 mRNA induction. This study suggests a role of c-FOS in regulating bsp70 mRNA induction.
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PMID:c-fos antisense oligonucleotide prevents delayed induction of hsp70 mRNA after soman-induced seizures. 922 58


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