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)

In neonates, asphyxia is a common cause of neuronal injury and often results in seizures. The authors evaluated whether blockade of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors during asphyxia and early recovery with 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo-(F)-quinoxaline (NBQX) ameliorates neurologic deficit and histopathology in 1-week-old piglets. Anesthetized piglets were exposed to a sequence of 30 minutes of hypoxia, 5 minutes of room air ventilation, 7 minutes of airway occlusion, and cardiopulmonary resuscitation. Vehicle or NBQX was administered intravenously before asphyxia (30 mg/kg) and during the first 4 hours of recovery (15 mg/kg/h). Neuropathologic findings were evaluated at 96 hours of recovery by light microscopic and cytochrome oxidase histochemical study. Cardiac arrest occurred at 5 to 6 minutes of airway occlusion, and cardiopulmonary resuscitation restored spontaneous circulation independent of treatment modalities in about 2 to 3 minutes. Neurologic deficit over the 96-hour recovery period was not ameliorated by NBQX. Seizure activity began after 24 to 48 hours in 7 of 10 animals with vehicle and in 9 of 10 of animals with NBQX. In each group, four animals died in status epilepticus. Neuropathologic outcomes were not improved by NBQX. The density of remaining viable neurons was decreased in parietal cortex and putamen by NBQX treatment. Metabolic defects in cytochrome oxidase activity were worsened by NBQX treatment. Seizure activity during recovery was associated with reduced neuronal viability in neocortex and striatum in piglets from both groups that survived for 96 hours. This neonatal model of asphyxic cardiac arrest and resuscitation generates neurologic deficits, clinical seizure activity, and selective damage in regions of basal ganglia and sensorimotor cortex. In contrast to other studies in mature brain, AMPA receptor blockade with NBQX failed to protect against neurologic damage in the immature piglet and worsened postasphyxic histopathologic outcome in neocortex and putamen.
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PMID:Effects of the AMPA receptor antagonist NBQX on outcome of newborn pigs after asphyxic cardiac arrest. 1045

The lithium-pilocarpine (Li-Pilo) model of epilepsy reproduces some pathophysiological, temporal, and developmental features of human temporal lobe epilepsy. In this model, rates of cerebral glucose utilization measured by the [(14)C]2-deoxyglucose technique increased during the initial status epilepticus (SE) and decreased during the latent or chronic periods. To correlate these metabolic changes with the activities of the enzymes of the glycolytic and tricarboxylic acid cycle pathways, we measured by histoenzymology the regional activity of two key enzymes of glucose metabolism, lactate dehydrogenase (LDH) for the anaerobic pathway and cytochrome oxidase (CO) for the aerobic pathway coupled to oxidative phosphorylation, at various times after SE induced by Li-Pilo in 10- (P10), 21-d-old (P21) and adult rats for CO and in adult rats only for LDH. CO activity was slightly affected in P10 and P21 rats only at 4 and 24 h and normalized by 14 d after SE. In adult rats, CO activity decreased at 4 and 24 h in damaged areas, like entorhinal cortex, hippocampal CA3 area, amygdala, and thalamus. At 14 d after SE, CO activity was decreased only in entorhinal cortex and increased in brainstem regions involved in the remote control of seizures. In adult rats, LDH activity decreased at 24 h and 14 d after SE in sensorimotor and entorhinal cortex. These data show that the enzymatic equipment underlying the metabolism of glucose is not severely affected by Li-Pilo SE and confirm our previous observations concerning the relative metabolic hyperactivity of brain regions involved in the seizure circuit despite marked neuronal loss.
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PMID:Postnatal maturation of cytochrome oxidase and lactate dehydrogenase activity and age-dependent consequences of lithium-pilocarpine status epilepticus in the rat: a regional histoenzymology study. 1529 83

Mitochondrial abnormalities have been associated with several aspects of epileptogenesis, such as energy generation, control of cell death, neurotransmitter synthesis, and free radical (FR) production. Increased production of FRs may cause mtDNA damage leading to decreased activities of oxidative phosphorylation complexes containing mtDNA-encoded subunits. In this study, we investigated whether increased generation of FR during status epilepticus would be sufficient to provoke abnormalities in mtDNA and in the expression and activity of cytochrome c oxidase (CCO), complex IV of the respiratory chain, in the chronic phase of the pilocarpine model of temporal lobe epilepsy. DNA analysis revealed low amounts of a 4.8 kb mtDNA deletion but with no differences in frequency or quantity in the control and experimental groups. We did not find abnormalities in the expression and distribution of an mtDNA-encoded subunit of CCO (CCO-I) or a relative decrease in CCO-I when compared with nuclear-encoded subunits (CCO-IV and SDH-fp). No abnormality in CCO activity was observed through histochemistry. Although evidences of mitochondrial abnormalities were found in previously published studies, our results do not suggest that the FRs, generated during the acute phase, determined important abnormalities in mtDNA, in expression of CCO-I, and in CCO activity.
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PMID:Investigation of mitochondrial involvement in the experimental model of epilepsy induced by pilocarpine. 1633 77

Present studies were carried out to decipher seizure-dependent changes in mitochondrial function and ultrastructure in rat hippocampus after status epilepticus (SE) induced by pilocarpine (PILO). Discernible mitochondrial ultrastructural damage was observed in the hippocampus. Enzyme assay revealed cytochrome oxidase (COX) activity significantly increased 3h after SE, decreased 7 d and 45 d after SE, whereas succinate dehydrogenase (SDH) activity displayed no significant changes. Quantitative real-time PCR and Western blotting showed that COX III (mitochondrial-encoded) mRNA and protein level were significantly increased at 3h, decreased to the control level on 7d and dropped significantly on 45 d; the corresponding expression of COX IV were not changed by PILO at any time tested. The results were also supported by immunohistochemistry. Thus, our results demonstrate that dysfunction of mitochondrial complex IV respiratory enzyme and mitochondrial ultrastructural damage in the hippocampus are associated with prolonged seizure during experimental temporal lobe epilepsy and mitochondria are more vulnerable to epileptic damage.
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PMID:Alteration of mitochondrial function and ultrastructure in the hippocampus of pilocarpine-treated rat. 2437 43

Cytochrome c oxidase (COX) deficiency is one of the most common respiratory chain deficiencies. A woman was presented at the age of 18y with acute loss of consciousness, non-convulsive status epilepticus, slow neurological deterioration, transient cortical blindness, exercise intolerance, muscle weakness, hearing loss, cataract and cognitive decline. Muscle biopsy revealed ragged-red fibers, COX negative fibers and a significant decreased activity of complex IV in a homogenate. Using next generation massive parallel sequencing of the mtDNA, a novel heteroplasmic mutation was identified in MTCO1, m.7402delC, causing frameshift and a premature termination codon. Single fiber PCR showed co-segregation of high mutant load in COX negative fibers. Mutation in mitochondrially encoded complex IV subunits should be considered in mitochondrial encephalomyopathies and COX negative fibers after the common mtDNA mutations have been excluded.
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PMID:Mitochondrial encephalomyopathy with cytochrome c oxidase deficiency caused by a novel mutation in the MTCO1 gene. 2495 8

Vertebrate respiratory chain complex III consists of eleven subunits. Mutations in five subunits either mitochondrial (MT-CYB) or nuclear (CYC1, UQCRC2, UQCRB, and UQCRQ) encoded have been reported. Defects in five further factors for assembly (TTC19, UQCC2, and UQCC3) or iron-sulphur cluster loading (BCS1L and LYRM7) cause complex III deficiency. Here, we report a second patient with UQCC2 deficiency. This girl was born prematurely; pregnancy was complicated by intrauterine growth retardation and oligohydramnios. She presented with respiratory distress syndrome, developed epileptic seizures progressing to status epilepticus, and died at day 33. She had profound lactic acidosis and elevated urinary pyruvate. Exome sequencing revealed two homozygous missense variants in UQCC2, leading to a severe reduction of UQCC2 protein. Deficiency of complexes I and III was found enzymatically and on the protein level. A review of the literature on genetically distinct complex III defects revealed that, except TTC19 deficiency, the biochemical pattern was very often a combined respiratory chain deficiency. Besides complex III, typically, complex I was decreased, in some cases complex IV. In accordance with previous observations, the presence of assembled complex III is required for the stability or assembly of complexes I and IV, which might be related to respirasome/supercomplex formation.
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PMID:Combined Respiratory Chain Deficiency and UQCC2 Mutations in Neonatal Encephalomyopathy: Defective Supercomplex Assembly in Complex III Deficiencies. 2880 36

Alpers' syndrome is an early-onset neurodegenerative disorder often caused by biallelic pathogenic variants in the gene encoding the catalytic subunit of polymerase-gamma (POLG) which is essential for mitochondrial DNA (mtDNA) replication. Alpers' syndrome is characterized by intractable epilepsy, developmental regression and liver failure which typically affects children aged 6 months-3 years. Although later onset variants are now recognized, they differ in that they are primarily an epileptic encephalopathy with ataxia. The disorder is progressive, without cure and inevitably leads to death from drug-resistant status epilepticus, often with concomitant liver failure. Since our understanding of the mechanisms contributing the neurological features in Alpers' syndrome is rudimentary, we performed a detailed and quantitative neuropathological study on 13 patients with clinically and histologically-defined Alpers' syndrome with ages ranging from 2 months to 18 years. Quantitative immunofluorescence showed severe respiratory chain deficiencies involving mitochondrial respiratory chain subunits of complex I and, to a lesser extent, complex IV in inhibitory interneurons and pyramidal neurons in the occipital cortex and in Purkinje cells of the cerebellum. Diminished densities of these neuronal populations were also observed. This study represents the largest cohort of post-mortem brains from patients with clinically defined Alpers' syndrome where we provide quantitative evidence of extensive complex I defects affecting interneurons and Purkinje cells for the first time. We believe interneuron and Purkinje cell pathology underpins the clinical development of seizures and ataxia seen in Alpers' syndrome. This study also further highlights the extensive involvement of GABAergic neurons in mitochondrial disease.
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PMID:Dissecting the neuronal vulnerability underpinning Alpers' syndrome: a clinical and neuropathological study. 3002 Oct 52