Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pilocarpine is a cholinergic agonist capable to induce seizures and an epilepticus-like state in rodents. This status epilepticus (SE) is an useful animal model to study the development and understanding of the neuropathology, behavioural and electroencephalographic alterations of human temporal lobe epilepsy. It has been suggested a relationship between SE and reactive oxygen species (ROS) that can result in seizure-induced neurodegeneration. The aim of this study was to evaluate the existence of oxidative damage and the changes in the antioxidant system in cortex after administration of a high pilocarpine dose. Rats were injected with pilocarpine (350 mg/kg i.p.) or with saline as control and 2h after the animals were sacrificed. Malondialdehyde (MDA) levels, as marker of lipid peroxidation, significantly increased (64%) after pilocarpine treatment evidencing oxidative damage. Antioxidant enzyme activities--catalase (CAT), glutathione peroxidase (GP) and superoxide dismutase (SOD)--significantly increased in response to pilocarpine (28%, 28% and 21%, respectively). GP and Mn-SOD gene expression were induced by pilocarpine treatment. Vitamin E concentration in brain cortex decreased (15%) as result of pilocarpine administration. In conclusion, the high dose of pilocarpine, used in the present study, induces oxidative damage and increases antioxidant enzyme activities and expression in brain cortex. Moreover, increased lipid peroxidation produces the consumption of Vitamin E.
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PMID:Antioxidant response and oxidative damage in brain cortex after high dose of pilocarpine. 1720 54

We have previously shown that seizures induce the formation of F(2)-isoprostanes (F(2)-IsoPs), one of the most reliable indices of oxidative stress in vivo. Isofurans (IsoFs) are novel products of lipid peroxidation whose formation is favored by high oxygen tensions. In contrast, high oxygen tensions suppress the formation of F(2)-IsoPs. The present study determined seizure-induced formation of IsoFs and its relationship with cellular oxygen levels (pO2). Status epilepticus (SE) resulted in F(2)-IsoP and IsoF formation, with overlapping but distinct time courses in hippocampal subregions. IsoF, but not F(2)-IsoP formation coincided with mitochondrial oxidative stress. SE resulted in a transient decrease in hippocampal pO2 measured by in vivo electron paramagnetic resonance oximetry suggesting an early phase of seizure-induced hypoxia. Seizure-induced F(2)-IsoP formation coincided with the peak hypoxia phase, whereas IsoF formation coincided with the 'reoxygenation' phase. These results demonstrate seizure-induced increase in IsoF formation and its correlation with changes in hippocampal pO2 and mitochondrial dysfunction.
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PMID:Seizure-induced formation of isofurans: novel products of lipid peroxidation whose formation is positively modulated by oxygen tension. 1795 61

Status epilepticus (SE) can cause severe neuronal loss and oxidative damage. As peroxisome proliferator-activated receptor gamma (PPARgamma) agonists possess antioxidative activity, we hypothesize that rosiglitazone, a PPARgamma agonist, might protect the central nervous system (CNS) from oxidative damage in epileptic rats. Using a lithium-pilocarpine-induced SE model, we found that rosiglitazone significantly reduced hippocampal neuronal loss 1 week after SE, potently suppressed the production of reactive oxygen species (ROS) and lipid peroxidation. We also found that treatment with rosiglitazone enhanced antioxidative activity of superoxide dismutase (SOD) and glutathione hormone (GSH), together with decreased expression of heme oxygenase-1 (HO-1) in the hippocampus. The above effects of rosiglitazone can be blocked by co-treatment with PPARgamma antagonist T0070907. The current data suggest that rosiglitazone exerts a neuroprotective effect on oxidative stress-mediated neuronal damage followed by SE. Our data also support the idea that PPARgamma agonist might be a potential neuroprotective agent for epilepsy.
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PMID:Activation of cerebral peroxisome proliferator-activated receptors gamma exerts neuroprotection by inhibiting oxidative stress following pilocarpine-induced status epilepticus. 1828 12

Chelatable iron is an important catalyst for the initiation and propagation of free radical reactions and implicated in the pathogenesis of diverse neuronal disorders. Studies in our laboratory have shown that mitochondria are the principal source of reactive oxygen species production after status epilepticus (SE). We asked whether SE modulates mitochondrial iron levels by two independent methods and whether consequent mitochondrial dysfunction and neuronal injury could be ameliorated with a cell-permeable iron chelator. Kainate-induced SE resulted in a time-dependent increase in chelatable iron in mitochondrial but not cytosolic fractions of the rat hippocampus. Systemically administered N,N'-bis (2-hydroxybenzyl) ethylenediamine-N,N'-diacetic acid (HBED), a synthetic iron chelator, ameliorated SE-induced changes in chelatable iron, mitochondrial oxidative stress (8-hydroxy-2' deoxyguanosine and glutathione depletion), mitochondrial DNA integrity and hippocampal cell loss. Measurement of brain HBED levels after systemic administration confirmed its penetration in hippocampal mitochondria. These results suggest a role for mitochondrial iron in the pathogenesis of SE-induced brain damage and subcellular iron chelation as a novel therapeutic approach for its management.
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PMID:Chelation of mitochondrial iron prevents seizure-induced mitochondrial dysfunction and neuronal injury. 1898 91

Autophagy, a process of bulk degradation of cellular constituents through autophagosome-lysosomal pathway, is enhanced during oxidative stress. Whether autophagy is induced during status epilepticus (SE), which induces an excess production of reactive oxygen species (ROS) and leads to oxidative stress, is not established. We also sought to determine if pretreatment with Vitamin E reduced autophagy. We used pilocarpine to elicit SE in rats. The ratio of LC3 II to LC3 I and beclin 1 were used to estimate autophagy. We found that ratio of LC3 II to LC3 I and beclin 1 increased significantly at 2, 8, 16, 24 and 72 h, peaking at 24 h after SE onset. Pretreatment with Vitamin E partially inhibited autophagy by reducing LC3 II formation and de novo synthesis of beclin 1 at 24 h after seizures. These data show that autophagy is increased in rats with pilocarpine-induced SE, and Vitamin E have a partial inhibition on autophagy.
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PMID:Autophagy is upregulated in rats with status epilepticus and partly inhibited by Vitamin E. 1913 75

The mechanisms that induce epileptic activity and make it durable, leading to status epilepticus (SE), are poorly known. They probably result from an imbalance between the activating systems of neuronal depolarisation (excitatory amino acids release with postsynaptic N-methyl-d-aspartate [NMDA] receptor activation, spreading depolarisation following abnormal progression) and the inhibiting systems (GABAergic synapses). Status epilepticus leads to many direct and indirect cerebral disorders, as well as systemic disorders, with intertwined mechanisms and consequences. These disorders are more frequent in case of convulsive SE with generalized tonic-clonic seizures. Direct neuronal damage (selective neuronal loss and epileptogenesis) results mostly from excitotoxicity, which arises from enhanced and extended neuronal activation. Indirect neuronal damage results from the inability of the circulatory system to supply sufficient oxygen and glucose contribution compared to the high metabolism level of the highly depolarized and synchronized neurons. This energetic deficit is usually patent after 30 minutes of SE, when systemic compensation mechanisms (cardiac output increase) are exhausted. Understanding these pathophysiologic aspects is essential for effective treatment of SE.
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PMID:[Pathophysiologic basis of status epilepticus]. 1924

The systemic consequences of status epilepticus occur in two stages: the first stage is a hyperadrenergic period (high blood pressure, tachycardia, arrhythmia, hyperventilation, hypermetabolism, hyperthermia), the second stage a collapsus period, sometimes with acute circulatory failure, and hypoxemia. Symptomatic resuscitation aimed at restoring vital functions should be undertaken. Resuscitation must be started immediately before hospital transfer, by a trained emergency team. Respiratory care includes at least oxygen intake, but it can also require oral intubation (crash induction) and mechanical ventilation. The arterial blood gas objectives are SaO(2)> or =95%, and 35mmHg< or =PaCO(2)< or =40mmHg. Fluid and electrolyte care includes intravenous infusion of normal saline, with control of sodium and calcium levels as well as blood pH within normal limits. Heart rate and blood pressure must be monitored. Mean blood pressure must be kept between 70 and 90mmHg, first by means of plasma volume expansion, and then norepinephrine if necessary. Hyperthermia must be corrected to prevent further neuronal damage. Cerebromeningeal sepsis should be ruled out. Capillary glucose (most often elevated) must be corrected using a pre-established insulin infusion algorithm. Rhabdomyolysis is rare, but can result in hyperkaliemia, acidosis, and acute renal failure. In case of associated intracranial hypertension (traumatic, vascular or infectious injury), status epilepticus is considered as a secondary insult for the brain, that can worsen neuronal damage. Numerous compounds have experimental neuroprotective properties, but none have proven significant efficacy in clinical conditions. Nevertheless, convulsion cessation is considered as a neuroprotective measure.
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PMID:[Non specific treatment of status epilepticus]. 1924 65

Seizures and status epilepticus induce an excessive production of reactive oxygen species leading to oxidative stress. Vitamin E, a classic antioxidant, has a neuroprotective effect on rats with seizures by regulating reactive oxygen species production. The activity of chaperone-mediated autophagy, a selective pathway for the degradation of cytosolic proteins in lysosomes, is enhanced during oxidative stress. Whether chaperone-mediated autophagy is induced during status epilepticus is not established. To address this problem, we used pilocarpine to elicit status epilepticus in rats. Lysosome-associated membrane protein 2a was used to estimate chaperone-mediated autophagy. We showed that compared to control animals, lysosome-associated membrane protein 2a at lysosomal membranes increased significantly in rats at 8 h, 16 h, and 24 h after induction of status epilepticus, which directly correlated with chaperone-mediated autophagy activity. Since reactive oxygen species are believed to be important in the pathogenesis of status epilepticus and are essential for the process of chaperone-mediated autophagy, we also sought to determine if pretreatment with vitamin E reduced chaperone-mediated autophagy. Pretreatment with vitamin E reduced oxidative stress and partially inhibited chaperone-mediated autophagy in brain at 24 h after status epilepticus versus vehicle. Taken together, these data show that chaperone-mediated autophagy is increased in rats with pilocarpine-induced status epilepticus through upregulation of de novo synthesis of lysosome-associated membrane protein 2a. Antioxidants such as vitamin E may partially inhibit activated chaperone-mediated autophagy.
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PMID:Vitamin E inhibits activated chaperone-mediated autophagy in rats with status epilepticus. 1927 30

Pilocarpine (PC), a muscarinic receptor agonist, is used for the induction of experimental models of status epilepticus (SE) for studying the type of seizure-induced brain injury and other neuropathophysiological mechanisms of related disorder. PC was administered to day-old Taiwan Native Breeder chicks and induced severe prolonged seizures (PC+PS) and repeated seizures (PC+RS) during 4h behavioral observations. Results showed that PC+PS group had excessive levels of reactive oxygen species (ROS) and malondialdehyde (MDA) production and lower activities of superoxide dismutase (SOD) and catalase (CAT) compared to the PC+RS group (p<0.05). Neuronal death and single strand DNA were significantly increased in dissociated brain cells of PC+PS group compared to that in the PC+RS group (p<0.01). Furthermore, a decrease in mitochondrial membrane potential (MMP) was observed in PC+PS group as compared with that in PC+RS group indicating neuronal mitochondrial dysfunction in PS group not in RS group. ROS, mitochondrial dysfunction and DNA damage played important roles in pathophysiology of the immature brain to prolonged-seizure-induced damage. A manifest result of depleted enzymatic antioxidants (SOD and CAT) was also contributed for the vulnerability of the neonatal brain to prolonged-seizure-induced oxidative damage. The replenishment of SOD and CAT activities might be useful in protecting brain against prolonged-seizure-induced neuronal death.
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PMID:The effects of pilocarpine-induced status epilepticus on oxidative stress/damage in developing animals. 1934 87

The relationship between free radical and scavenger enzymes has been found in the epileptic phenomena and reactive oxygen species have been implicated in seizure-induced neurodegeneration. Using the epilepsy model obtained by systemic administration of pilocarpine in rats, we investigated the lipid peroxidation, nitrite content, superoxide dismutase (SOD) and catalase activities in the hippocampus of rats during chronic period. The enzyme activities as well as the lipid peroxidation and nitrite concentrations were measured using spectrophotometric methods and the results compared to values obtained from saline-treated animals. The superoxide dismutase and catalase activities increased during the chronic phase. In addition, lipid peroxidation and nitrite levels increased in same period in the hippocampus of animals observed during spontaneous recurrent seizures. Previous studies showed that animals presenting seizures and submitted to 24h of status epilepticus showed normal levels of superoxide dismutase and increased in catalase activities as well as an increase in hippocampal lipid peroxidation and nitrite concentrations. These results show a direct evidence of lipid peroxidation and nitrite during seizure activity that could be responsible for neuronal damage in the hippocampus of rats, during the establishment of pilocarpine model of epilepsy.
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PMID:Investigation of oxidative stress involvement in hippocampus in epilepsy model induced by pilocarpine. 1961 71


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