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

We examined the effects of generalized seizures on heat shock protein (hsp) mRNA induction in the rat brain using in situ hybridization. Seizures induced by electroconvulsive shock, electrical or cocaine kindling caused a selective induction of the constitutive hsp 73 gene in the dentate gyrus. In these seizure paradigms, not thought to induce widespread tissue damage, neither the heat-inducible hsp 72 gene nor a member of the hsp 90 family (hsp 84) were induced. Hsp 73 may play a role in the adaptation and/or in the maintenance of dentate granule cell integrity following seizures.
 ...
PMID:Induction of constitutive heat shock protein 73 mRNA in the dentate gyrus by seizures. 131 15

Zinc is a potent inducer of the 72 kD heat shock protein (HSP72). In brain, pathological conditions such as ischemia and seizures increase extracellular zinc. The present study examines the effect of zinc on HSP72 expression in rat primary cortical astrocyte culture. Astrocytes were grown to confluence and exposed to zinc chloride in CO2-equilibrated Earle's buffered salt solution. Expression of HSP72 was examined using immunocytochemistry. HSP72 was induced with zinc concentrations of 5 to 100 microM after 4 h exposures, or 200 to 300 microM after 15 min exposures. At the lower concentrations expression occurred in small clusters of contiguous cells. At concentrations high enough to cause cell death, HSP72-positive astrocytes formed a continuous margin around patches of dead cells. These patterns of HSP72 expression are similar to the patterns seen after cerebral ischemia in vivo. Exposure to zinc at 100 microM for 4 h or 400 microM for 15 min caused greater than 90% cell death. Increases in extracellular zinc may contribute to HSP72 induction and astrocyte death under ischemia and other pathological conditions in brain.
 ...
PMID:Zinc toxicity and induction of the 72 kD heat shock protein in primary astrocyte culture. 133 69

The inducible 72 kDa heat shock protein (HSP72) has been shown to be protective in non-neuronal cells and neurons in culture, but its function and the control of its expression in the CNS are poorly understood. Although HSP72 is induced in neurons in vivo by neurotoxic compounds that produce seizures and neuronal damage, it is unknown if its expression is a specific response to excitation per se or to "stressful" or potentially injurious excitation, or if it is a marker or mediator of irreversible injury. We have attempted to identify the nature of the stimulus for HSP72 expression by utilizing focal electrical stimulation that can either excite or destroy postsynaptic cells, depending on the duration of afferent stimulation. Previous studies have demonstrated that intermittent stimulation of the main hippocampal afferent pathway for 24 hr evokes synchronous discharges in dentate granule cells but does not injure them. However, the same stimulation irreversibly destroys three of the four cell populations innervated by the granule cells. The three vulnerable populations are the dentate hilar mossy cells, the somatostatin/neuropeptide Y (NPY)-immunoreactive hilar neurons, and the CA3c pyramidal cells. The fourth and relatively resistant population is the GABA-immunoreactive dentate basket cells. In this study, we have localized HSP72 expression immunocytochemically in the hippocampal dentate gyrus in response to nontoxic durations of potentially neurotoxic afferent stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Heat shock protein expression in vulnerable cells of the rat hippocampus as an indicator of excitation-induced neuronal stress. 149 43

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.
 ...
PMID:Induction of heat shock (stress) genes in the mammalian brain by hyperthermia and other traumatic events: a current perspective. 209 76

The inducible 72-kDa heat shock protein (HSP72) is a highly conserved stress protein that is expressed in CNS cells and may play a role in protection from neural injury. We used a monoclonal antibody to HSP72 and immunocytochemistry to localize HSP72 in the rat brain 24 h following either 30 or 60 min of flurothyl-induced status epilepticus. Sprague-Dawley rats were anesthetized with halothane, paralyzed, and ventilated, and remained normotensive and well oxygenated for the duration of the seizures. Seizure activity was quantified via analysis of the scalp EEG pattern. HSP72-like immunoreactivity (HSP72-LI) was induced in specific brain regions in a graded fashion that correlated, in part, with the duration and degree of seizure activity. Milder seizures produced HSP72-LI limited to layers 2 and 3 of frontoparietal cortex, dentate hilus cells, and CA3 pyramidal neurons. More extensive seizures led to HSP72-LI in layers 2, 3 and 5 of frontoparietal and visual cortex, dentate hilus cells, CA1 and CA3 pyramidal neurons, and certain thalamic and amygdaloid nuclei. These are similar to many, but not all, of the brain regions known to be injured with this model. No HSP72-LI was observed in sham-treated controls or flurothyl-treated animals whose seizures were controlled with pentobarbital. HSP72-LI thus localizes to certain regions of seizure-induced injury, and may provide a sensitive method of detecting neuronal 'stress' or injury relatively soon after status epilepticus. Whether or not HSP72 synthesis plays a protective role in the pathogenesis of seizures, or is only a marker for cell injury, remains to be determined.
 ...
PMID:The pattern of 72-kDa heat shock protein-like immunoreactivity in the rat brain following flurothyl-induced status epilepticus. 228 19

Stargazer mutant mice inherit a recessive neuronal excitability phenotype featuring frequent non-convulsive spike-wave seizures that arise from synchronous bursting in neocortical, thalamic and hippocampal networks. Immunocytochemistry reveals that granule cells in the mutant dentate gyrus aberrantly express neuropeptide Y (NPY) at multiple ages following the developmental onset of seizures. The ectopic NPY is selectively concentrated in the mossy fibers, co-localizing with the releasable dense core vesicle pool. The NPY content of native NPY+local circuit neurons is also elevated in the mutant CNS. There is no concurrent elevation of hippocampal 72 kDa heat shock protein (HSP72), glial fibrillary acidic protein (GFAP) or NADPH-diaphorase, three markers that are induced during cellular injury, and no evidence of granule cell loss. Since mossy fiber NPY expression appears after the developmental onset of spike-wave discharges and can be induced in wild type granule cells by electrical stimulation, the altered peptide phenotype is likely to reflect transynaptic gene induction triggered by synchronous bursting. These results link a specific pattern of repetitive synaptic input with selective molecular plasticity in dentate granule cells that may contribute to dynamic modifications in hippocampal network excitability.
 ...
PMID:Aberrant expression of neuropeptide Y in hippocampal mossy fibers in the absence of local cell injury following the onset of spike-wave synchronization. 747 19

Kainic acid-induced seizures in the rat brain cause severe brain damage that is thought to result, in part, from oxidative stress. In this study, we examine the consequences of systemic administration of kainic acid on expression of several genes that encode proteins thought to play roles in protection from oxidative stress, including metallothionein-I, and -III. Kainic acid causes an increase in metallothionein-I and heme oxygenase-I mRNAs, as well as an increase in c-fos, heat shock protein-70, and interleukin-1 beta mRNAs. The induction of these mRNAs is seizure dependent, and is greater in brain areas with extensive damage (e.g. piriform cortex) than in areas with minimal damage (e.g. frontal cortex and cerebellum). In contrast, little or no change in mRNA for metallothionein-III, manganese superoxide dismutase, copper-zinc superoxide dismutase, glutathione-s-transferase ya subunit or glutathione peroxidase occur. The prolonged and robust concordant induction of the metallothionein-I and heme oxygenase-I genes may reflect the oxidative stress produced by kainic acid-induced seizures. In addition, the induction of interleukin-1 beta gene expression suggests an inflammatory response in brain regions damaged by kainic acid-induced seizures. Delineating the regulation of genes associated with oxidative and inflammatory responses can contribute to a fuller understanding of seizures and associated brain damage.
 ...
PMID:Temporalspatial patterns of expression of metallothionein-I and -III and other stress related genes in rat brain after kainic acid-induced seizures. 765 48

Induction of heat shock/stress proteins is a key feature of a universal mechanism of cellular defence to injury known as the "stress response". The present study investigated whether heat shock protein expression correlates with the extent of neuronal injury inflicted by increasingly intense seizure activity. Limbic epilepsy was elicited by injecting intraperitoneally 8, 10 or 12 mg/kg kainic acid in adult Sprague-Dawley rats, resulting in graded degrees of seizure intensity and duration that closely correlated with the respective dose. Stress protein expression was investigated by immunocytochemistry and western blot analysis of microdissected brain areas with specific antibodies directed against representative members of three major classes of stress proteins, i.e. heat shock protein 72, heat shock protein 90 and heat shock protein 27, respectively. Heat shock protein 72 was absent in the brains of control animals, but markedly induced after limbic seizures in neurons of the limbic system, cortex, striatum and thalamus, with peak levels at 24 h. An increasing degree of seizure intensity caused a graded increase of heat shock protein 72 levels with a sequence reflecting the rank order of kainic acid susceptible hippocampal subpopulations. In contrast to heat shock protein 72, heat shock protein 90 was markedly expressed and equally abundant in all brain areas of untreated control animals and at any time point investigated following limbic seizures. Heat shock protein 27 was not detected in the brain of untreated animals nor following epilepsy. The present investigations demonstrate that the induction threshold of heat shock protein 72 in specific neuronal subpopulations clearly correlates with seizure intensity and duration. In addition, our experiments also define a narrow range of heat shock protein 72 expression with an upper limit beyond which heat shock protein 72 synthesis sharply declines. These findings reflect the risk of hippocampal neurons to undergo limbic seizure induced neuronal degeneration. It remains to be determined whether heat shock protein 72 expression is only a valuable marker for reversible neuronal injury or actually confers a neuroprotective effect.
 ...
PMID:Correlation between seizure intensity and stress protein expression after limbic epilepsy in the rat brain. 775

Limbic seizures may be under the regulation of the substantia nigra, pars reticulata (SNpr). Using microinjection of the NMDA antagonist AP7, we investigated the role of SNpr in modulating seizures induced by kainic acid. Seizure severity was analyzed electrographically and neural injury assessed by measurement of heat shock protein (HSP) expression and acid fuchsin (AF) staining of vulnerable hippocampal cells. Intranigral injection of AP-7 increased the duration of electrographic seizure discharges and the number of HSP-positive and acid fuchsin stained cells in all hippocampal sectors, suggesting that blockade of the NMDA receptors in SNpr enhanced neural injury.
 ...
PMID:Bilateral intranigral NMDA blockade increases status duration and neuronal injury from systemic kainic acid. 782 Jun 87

The substantia nigra pars reticulosa (SNpr) is involved in the initiation and propagation of seizures within the limbic system (cingulate and parahippocampal gyri and associated connections in the brain stem, e.g. amygdala, hypothalamus, some thalamic nuclei, and parts of basal ganglia). We have investigated the pattern of neuronal injury (using heat shock protein (HSP) expression) and cell death (acid-fuchsin (AF) staining) in SNpr and limbic structures following seizures evoked by bilateral intranigral injection of kainic acid. Affected cells were observed predominantly in piriform cortex, amygdala, hippocampal formation, and thalamic nuclei; massive necrosis or hemorrhage occurred in bilateral piriform cortices following prolonged seizures. The piriform cortex may play an important role in the activation of limbic seizures under the regulation of the SNpr.
 ...
PMID:The pattern of neuronal injury following seizures induced by intranigral kainic acid. 783 Sep 48


1 2 3 4 5 Next >>