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

The cerebral protective effect of eptazocine, an opioid mu-antagonist-kappa-agonist, was investigated using mice and rats subjected to ischemia. 1) Decapitation or concussive head injury (20 g, 30 cm)-induced ischemia in mice: Eptazocine (3,10 mg/kg) prolonged the gasping duration or the survival time in a dose-dependent manner. 2) Ischemic brain edema induced by bilateral carotid arterial occlusion (BLCO) in rats: Administration of eptazocine just after BLCO treatment significantly prevented the incidence of ischemic seizures, lethality and an increase in cerebral water content. 3) Acute ischemic changes in cerebral energy metabolism in mice: 2-min BLCO treatment decreased the cerebral contents of phosphocreatine and ATP, and it increased the contents of AMP and lactate, resulting in a 34% decrease in energy charge potential and an increase in lactate/pyruvate ratio. Such changes were improved by eptazocine (3, 10 mg/kg) and ethylketocyclazocine (3 mg/kg), a kappa-agonist. 4) Respiratory function in mouse brain mitochondria preparations: Eptazocine increased the State 3 respiration and respiratory control index (RCI:State 3/State 4), and it prevented a decrease in RCI induced by 3-min ischemia. These results suggest that eptazocine may improve cerebral ischemic disorders through an activation and/or protection of mitochondrial energy-producing systems.
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PMID:[Protective effect of eptazocine, a novel analgesic, against cerebral ischemia in mice and rats]. 205 80

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

Seizures are a documented complication to cerebral ischemia. After 10 min of forebrain ischemia in rats, preischemic hyperglycemia invariably leads to severe, most often fatal epileptic attacks. This outcome is related to the exaggerated lactic acidosis, which has been suggested as a possible contributor to severe membrane changes and widespread edema. To find out if circulating hormones or plasma energy substrates modulate this additive damage caused by the hyperglycemia, plasma concentrations of of corticosterone, epinephrine, norepinephrine, dopamine, glucagon, insulin, glucose, free fatty acids (FFA), 3-hydroxybutyrate, and acetoacetate were measured before and in the early recirculation period after 15 min of forebrain ischemia in the rat. Plasma corticosterone levels did not differ between the normo- and hyperglycemic groups. Although not significantly different from control, the catecholamine levels showed a tendency to be higher in the hyperglycemic groups. Therefore, because catecholamines have been reported to have a protective effect during ischemia the present result cannot explain why hyperglycemia aggravates the ischemic damage. Insulin levels seemed to increase during ischemia but not significantly. Levels quickly returned to normal after 30 min of recirculation. FFA concentrations were reduced after the induction of ischemia and appeared lower in all hyperglycemic groups. The level of one of the ketone bodies, 3-hydroxybutyrate, showed a significant decrease in hyperglycemic ischemia in all groups compared with normoglycemic ischemia. The same tendency was seen for acetoacetate. Results are compatible with a protective role of ketone bodies in ischemia. It is concluded that among the hormones and substrates studied only the ketone body concentrations qualify as a modulator of the exaggerated brain damage after ischemia in hyperglycemic subjects.
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PMID:Ischemia in normoglycemic and hyperglycemic rats: plasma energy substrates and hormones. 211 Apr 23

Localized in vivo proton magnetic resonance spectra obtained from diseased areas in 2 patients with chronic localized encephalitis (Rasmussen's syndrome) showed reduced resonance intensities from N-acetyl compounds, suggesting focally decreased N-acetylaspartate concentrations. One of the patients had epilepsia partialis continua secondary to the encephalitis. In this patient, the spectra demonstrated a high lactate resonance intensity (not seen in the normal, contralateral hemisphere) corresponding to an estimated local concentration of about 7.5 mM. We speculate that the observed decrease in the N-acetyl compound resonance may be a biochemical correlate of the neuronal loss characteristic of this disease. The results establish that excessive accumulation of lactate can occur in the human brain as a result of seizure activity even in the absence of ischemia. Thus, bioenergetic compromise may be 1 predisposing factor to the death of excitable cells in the epileptogenic area.
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PMID:A proton magnetic resonance spectroscopy study of focal epilepsy in humans. 211 99

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

Unilateral carotid ligation in immature rats, followed by 2 h of hypoxia led to ischemic cell change from 2 h after the insult, on the ligated side of the brain. There was a time-dependent induction of immunoreactive c-fos protein in neurones but not glia or ependyma on the non-ligated side of the brain. Induction only occurred in rats that had seizures post hypoxia-ischemia. In the ligated hemisphere c-fos protein was induced in glial-like cells in the corpus callosum, fornix/fimbria and internal capsule and in ependymal cells lining the lateral ventricle starting from 2 h after hypoxia but subsiding by 3 days. No neuronal c-fos induction was seen in areas showing neuronal damage. MK-801 or carbamazepine, which prevented hypoxia-ischemia-induced seizures, also prevented c-fos induction in the non-ligated hemisphere while MK-801 was associated with increased c-fos induction in hippocampal neurones from the ligated side, as well as in glial-like and ependymal cells. These results suggest several processes are involved following the hypoxic-ischemic insult. Firstly, severe hypoxia-ischemia is associated with a reduction in neuronal c-fos protein levels, probably as a result of neuronal failure and death. Secondly, post hypoxic seizures cause c-fos induction in surviving neurones. Thirdly, glial-like from regions in which there is neural loss also exhibit induction of c-fos, which may be important for their subsequent proliferation or for the production of growth factors.
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PMID:Effects of hypoxia-ischemia and seizures on neuronal and glial-like c-fos protein levels in the infant rat. 212 69

Transient ischemia in normoglycemic animals leads to delayed neuronal damage which is confined to selectively vulnerable regions. In at least one of these, the CA1 sector of the hippocampus, cell death is preceded by neuronal hyperactivity, presumed to be caused by loss of inhibitory control. Hyperglycemic subjects develop postischemic seizures, and show enhanced damage. The ATP-sensitive K+ channel, which may be important in inhibitory control, is the target of antidiabetic sulfonylureas. We determined densities of sulfonylurea binding sites in rat brain after forebrain ischemia. Normoglycemic animals showed a decrease of glibenclamide receptor binding in the CA3 field, hilus and dentate gyrus of the hippocampus after 1 day of recovery. After 4 days of recovery, levels of sulfonylurea binding sites decreased mainly in the CA1 field and in the hilus, as well as in the substantia nigra. After 1 day of recovery, hyperglycemic animals did not show any significant variations of densities of sites compared to control animals. It is proposed that reduction of inhibitory control by ATP-sensitive K+ channels may be associated with delayed neuronal death.
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PMID:Brain ischemia alters the density of binding sites for glibenclamide, a specific blocker of ATP-sensitive K+ channels. 212 31

We have analyzed the brain pattern and time-course of c-fos-like proteins expression in kainic acid-induced seizures in the rat. C-fos-like immunoreactivity increased initially in the hippocampus, notably in the dentate gyrus, at the time of the first limbic motor seizure (90 min after kainate). C-fos-like labelling progressively involved different structures of the limbic system when the rats manifested a permanent epileptic state (3-6 h). The labelling was still conspicuous 12 h after kainate treatment and progressively declined to reach control levels 48 h after kainate. This time-course is similar to that produced by kainic acid on 2-deoxyglucose consumption and correlates with the electrographic changes previously described, supporting the idea that c-fos-like immunostaining may provide a useful marker of neuronal activity, with a cellular resolution. Since anoxic-ischemic treatment produces a very slight and transient increase in c-fos-like immunostaining restricted to the fascia dentata, c-fos-like expression is seizure-related and not due to a local hypoxia or ischemia.
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PMID:Effects of kainic acid-induced seizures and ischemia on c-fos-like proteins in rat brain. 212 98

Kainic acid (KA) is a potent neuroexcitatory drug widely used in the experimental study of seizure activity. Subcutaneous injection of KA into rats (10 mg/kg in saline 10 mg/ml; pH 7.0) induced longlasting status epilepticus followed by damage of CNS tissue in the entorhinal/pyriform cortex and in the hippocampus. The studies covered by this report demonstrated the formation of cytotoxic brain edema characterized by massive swelling of perineuronal and perivascular astroglia with microcirculation disturbance after KA injection, resulting in parenchymal necrosis of the affected region; furthermore perivenous hemorrhages and necroses corresponding to herniation lesions of the brain appear. Tracer studies with Na-fluorescein, Evans blue, albumin, and horseradish peroxidase revealed only a mild increase in the permeability of cerebral vessels, topographically unrelated to areas of brain edema. Treatment of brain edema with dexamethasone did not influence the incidence and severity of edematous brain damage. Treatment with mannitol, however, completely prevented the lesion in 54% of animals injected with KA. The present results indicate that brain edema plays an important role in the pathogenesis of epileptic brain damage following systemic KA intoxication. It is suggested that in this model brain edema develops due to massive ionic imbalance caused by KA induced persistent neuronal excitation. In addition the model demonstrates the possible pathogenetic role of selective astrocytic swelling in the production of local hippocampal ischemia followed by herniation and its sequels. Such pathology originating from astrocytes probably may occur also in closed brain injury.
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PMID:Some mechanisms of brain edema studied in a kainic acid model. 213 Jun 48

The adrenal stress hormones glucocorticoids (GCs) impair the ability of hippocampal neurons to survive neurological insults, including hypoxia-ischemia and seizure. These insults are thought to be toxic via a cascade of excessive synaptic concentrations of excitatory neurotransmitters (e.g. glutamate), activation of the NMDA receptor, and pathologic mobilization of cytosolic calcium post-synaptically. We tested whether GCs exacerbate these insults by exacerbating this 'NMDA cascade'. We sought a toxin which damaged independently of the NMDA cascade, and whose toxicity was enhanced by GCs. After testing a number of neurotoxins, we found that the antimetabolite 3-acetylpyridine (3AP) fit this requirement. We then tested if blockade of the NMDA receptor blocks the ability of GCs to enhance 3AP toxicity. Hippocampi were microinfused with 160 micrograms of 3AP. Elevating circulating GC concentrations to the range seen during major stressors for a week before and after microinfusion caused a significant increase in 3AP-induced damage (when compared to adrenalectomized rats kept GC-free for the same period). Infusing the NMDA receptor blocker APV with 3AP did not alter the toxicity in adrenalectomized rats. However, APV reduced 3AP-induced damage in GC-treated rats to levels seen in adrenalectomized rats. This suggests that GCs endanger hippocampal neurons by enhancing glutamatergic signals and/or enhancing vulnerability to such signals. As a possible explanation for this observation, GCs inhibit glucose uptake into hippocampal neurons, and numerous steps in the NMDA cascade are exacerbated when neuronal energy stores are diminished.
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PMID:Glucocorticoid endangerment of hippocampal neurons is NMDA-receptor dependent. 214 1


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