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)

During seizure-like events (SLEs), intracellular Ca2+ concentration ([Ca2+]i) increases causing depolarization of the mitochondrial membrane and subsequent intramitochondrial accumulation of Ca2+. Mitochondrial depolarization results in an interruption of oxidative phosphorylation and increase in reactive oxygen species. Calcium activates enzymes of the citrate cycle. A characteristic feature of the low-Mg2+-induced SLEs is that they are transformed to a late activity refractory to anticonvulsant drugs, which may be regarded as a model system of difficult to treat status epilepticus. In contrast, 4-aminopyridine (4-AP)-induced activity rarely evolves to such late activity. The autofluorescence of NAD(P)H was used to monitor changes in cellular energy metabolism in the entorhinal cortex in two in vitro models of focal epilepsy. During repetitive 4-AP-induced SLEs there was a short decrease followed by a long-lasting overshoot of the NAD(P)H signal. This sequence remained unaltered during recurring SLEs. In contrast, during recurrent low-Mg2+-induced SLEs, the brief initial NADH signal reduction was unchanged but the following overshoot of NADH displayed a continuous decrease. This indicates a relative energy failure, which may contribute to the transformation to late activity in the low-Mg2+ model.
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PMID:A relative energy failure is associated with low-Mg2+ but not with 4-aminopyridine induced seizure-like events in entorhinal cortex. 991

The protective blood-brain barrier normally allows diffusion of small molecules such as oxygen and carbon dioxide, and transport of essential nutrients, but excludes large proteins and other blood constituents from the interstitial space of the CNS. However, head trauma, stroke, status epilepticus and other pathological conditions can all compromise the integrity of this barrier, and allow blood proteins as large as albumin to gain access to the extracellular spaces that surround neurons and glia. Given their possible entry into brain tissue during cerebrovascular insult, the effects of blood-derived proteases such as thrombin, tissue plasminogen activator and plasmin in the CNS have come under increasing scrutiny. Evidence now supports a role for serine proteases in the sequence of events that can lead to glial scarring, edema, seizure and neuronal death.
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PMID:Serine proteases and brain damage - is there a link? 1126 39

Neuroemergencies are life-threatening situations in which, whatever the cause, common pathologic phenomena result in secondary brain lesions. The goal of critical care management is to stop these self-aggravating processes as soon as possible. Initial resuscitation is devoted to control of the airway and hemodynamic and hydroelectrolytic stabilization. With mass lesions, minimal computed tomographic exploration immediately precedes surgical decompression. Further critical care adapted to the child's needs requires multimodal monitoring. Normoventilation, deep sedation, osmotherapy with mannitol or hypertonic saline solutions, and optimization of mean arterial pressure are the basis of management. A purely pressure-driven approach aimed at controlling cerebral perfusion pressure could be potentially harmful, and associated measurement of blood flow velocity with transcranial Doppler and jugular bulb oxygen saturation monitoring allows an approach to cerebral blood flow and metabolism. Outcome can be improved in dangerous situations such as severe brain injuries, cerebral arteriovenous malformation rupture, status epilepticus, and acute hydrocephalus, provided that emergency management could be applied efficiently.
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PMID:Pediatric neurologic emergencies. 1137 15

Status epilepticus (SE)-induced neuronal injury may involve excitotoxicity, energy impairment and increased generation of reactive oxygen species (ROS). Potential treatment therefore should consider agents that protect mitochondrial function and ROS scavengers. In the present study, we examined whether the spin trapping agent N-tertbutyl-alpha-phenylnitrone (PBN) and the antioxidant vitamin E (DL-alpha-tocopherol) protect levels of high-energy phosphates during SE. In rats, SE was induced by either of two inhibitors of acetylcholinesterase (AChE), the organophosphate diisopropylphosphorofluoridate (DFP, 1.25 mg/kg, sc)- or the carbamate carbofuran (1.25 mg/kg, sc). Rats were sacrificed 1 h or 3 days after onset of seizures by head-focused microwave (power, 10 kW; duration 1.7 s) and levels of the energy-rich phosphates adenosine triphosphate (ATP) and phosphocreatine (PCr) and their metabolites adenosine diphosphate (ADP) and adenosine monophosphate (AMP), and creatine (Cr), respectively, were determined in the cortex, amygdala and hippocampus. Within 1 h of seizure activity, marked declines were seen in ATP (34-60%) and PCr (25-52%). Total adenine nucleotides (TAN = ATP + ADP + AMP) and total creatine compounds (TCC = PCr + Cr) were also reduced (TAN 38-60% and TCC 25-47%). No changes in ATP/AMP ratio were seen. Three days after the onset of seizures, recovery of ATP and PCr was significant in the amygdala and hippocampus, but not in the cortex. Pretreatment of rats with PBN (200 mg/kg, ip, in a single dose), 30 min before DFP or carbofuran administration, prevented induced seizures and partially prevented depletion of high-energy phosphates. Pretreatment with the natural antioxidant vitamin E (100 mg/kg, ip/day for 3 days), partially prevented loss of high energy phosphates without affecting seizures. In controls, citrulline, a product of nitric oxide synthesis, was found to be highest in the amygdala, followed by hippocampus, and lowest in the cortex. DFP- or carbofuran-induced seizures caused elevation of citrulline levels seven- to eight-fold in the cortex and three- to four-fold in the amygdala and hippocampus. These results suggest a close relationship between SE, excitotoxicity and energy metabolism. The involvement of oxidative stress is supported by the findings that DFP and carbofuran trigger an excessive nitric oxide (NO) production in the seizure relevant regions of the brain.
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PMID:Depletion of energy metabolites following acetylcholinesterase inhibitor-induced status epilepticus: protection by antioxidants. 1140 58

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 (PILO) in rats, we investigated the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities as well as the hydroperoxide (HPx) concentration in the hippocampus of rats during status epilepticus (SE), silent and chronic periods. The enzyme activities as well as the HPx concentration were measured using spectrophotometric methods and the results compared to values obtained from saline-treated animals. The SOD activity decreased after long-lasting SE period and during the chronic phase. In addition, HPx levels increased in same periods whereas the GPx activity increased only in the hippocampus of animals submitted to 1 h of SE. Animals presenting partial seizures, those submitted to 5 h of SE and animals from the silent period (seizure free) showed normal levels of SOD, GPx and HPx. These results show a direct evidence of lipid peroxidation during seizure activity that could be responsible for neuronal damage in the hippocampus of rats, during the establishment of PILO model of epilepsy.
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PMID:Superoxide dismutase, glutathione peroxidase activities and the hydroperoxide concentration are modified in the hippocampus of epileptic rats. 1146 13

Acute bacterial meningitis (ABM) in children is associated with a high rate of acute complications and mortality, particularly in the developing countries. Most of the deaths occur during first 48 hours of hospitalization. Coma, raised intracranial pressure (ICP), seizures, shock have been identified as significant predictors of death and morbidity. This article reviews issues in critical care with reference to our experience of managing 88 children with ABM in PICU. Attention should first be directed toward basic ABCs of life-support. Children with Glasgow Coma Scale (GSC) score < 8 need intubation and supplemental oxygen. Antibiotics should be started, even without LP (contraindicated if focal neuro-deficit, papilledema, or signs of raised ICP). Raised ICP is present in most of patients; GCS < 8 and high blood pressure are good guides. Mannitol (0.25 gm/Kg) should be used in such patients. If there are signs of (impending) herniation short-term hyperventilation is recommended; prolonged hyperventilation (> 1 hour) must be avoided. Any evidence of poor perfusion, hypovolemia and/or hypotension needs aggressive treatment with normal saline boluses and inotropes, if necessary, to maintain normal blood pressure. Empiric fluid restriction is not justified. Seizures may be controlled with intravenous diazepam or lorazepam. Refractory status epilepticus may be treated with continuous diazepam (0.01-0.06) mg/kg/min) or midazolam infusion. Ventilatory support may be needed early for associated pneumonia, poor respiratory effort and/or coma, and occasionally to reduce work of breathing in shock. Provision of critical care to children with ABM may reduce the mortality significantly as experienced by us.
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PMID:Bacterial meningitis in children: critical care needs. 1156 52

This study was undertaken to clarify whether seizures in the newborn cause damage to the healthy brain and, more specifically, to determine the extent to which seizures may contribute to the brain-damaging effects of hypoxia-ischemia (HI). Seizures were induced in 10-d-old rat pups with kainic acid (KA). Seizure duration was determined electrographically. HI was induced by common carotid artery ligation followed by exposure to 8% oxygen for either 15 or 30 min. Six groups of animals were assessed: 1) controls [neither KA nor HI (group I)]; 2) group II, KA alone; 3) group III, 15 min HI alone; 4) group IV,15 min HI plus KA; 5) group V, 30 min HI alone; and 6) group VI, 30 min HI plus KA. Animals were assessed neuropathologically at 3 (early) and 20 (late) d of recovery. KA injection without hypoxia resulted in continuous clinical and electrographic seizures lasting a mean of 282 min. No neuropathologic injury was seen in groups I (no HI or KA), II (KA alone), III (15 min HI alone), or IV (15 min HI and KA). Animals in group V (30 min HI alone) displayed brain damage with a mean score of 2.3 and 0.60 at 3 and 20 d of recovery, respectively. Animals in group VI (30 min HI and KA) had a mean score of 12.1 and 3.65 at 3 and 20 d of recovery, respectively. Compared with group V, the increased damage as a result of the seizure activity in group VI occurred exclusively in the hippocampus. Status epilepticus in the otherwise "healthy" neonatal brain does not cause neuropathologic injury. However, seizures superimposed on HI significantly exacerbate brain injury in a topographically specific manner.
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PMID:Prolonged seizures exacerbate perinatal hypoxic-ischemic brain damage. 1156 86

Three cases involving a previously unreported association of acute pancreatic damage following convulsive status epilepticus (SE) are presented. A review of literature failed to reveal a similar association between SE and acute pancreatic damage. As possible pathophysiological mechanisms of this so far unknown sequel of SE, increased intraduodenal pressure during SE leading to the reflux of the duodenal contents into the pancreatic duct, along with altered metabolism of oxygen-derived free radicals during a prolonged seizure with hypoxia and ischemia resulting in acinar cell injury are suggested. We believe that SE should be considered as an additional risk factor of acute pancreatitis and that pancreatic enzymes should be monitored in patients who have prolonged seizures.
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PMID:Acute pancreatic damage associated with convulsive status epilepticus: a report of three cases. 1173 95

Experimental data indicate that acute hyperglycaemia can aggravate the consequences of epileptic seizures on the permeability of the blood-brain barrier (BBB). The purpose of this study was to examine the effects of chronic administration of alpha -tocopherol (vitamin E) and acute catalase administration on the disrupted BBB during experimentally pentylenetetrazole-induced status epilepticus in acute hyperglycaemic rats. The integrity of the BBB was tested using the Evans Blue (EB) dye extravasation. The concentration of EB dye was measured in four regions of the brain. Epileptic seizures induced a significant increase in EB dye extravasation in the brain regions compared with that of the groups of rats treated with saline, glucose, catalase and alpha -tocopherol (P< 0.01). The content of EB dye in the brain regions of animals in the acute hyperglycaemia plus epileptic group was higher than that of the saline, glucose, catalase, alpha -tocopherol and epileptic groups (P< 0.01). The increased EB dye transfer from blood to the brain in status epilepticus and acute hyperglycaemia plus status epilepticus was attenuated by the treatment with catalase and alpha -tocopherol. These data suggest that a partial reduction in the production of reactive oxygen species by catalase and alpha -tocopherol contributes to decreases in the content of EB dye across the BBB during pentylenetetrazole-induced status epilepticus in acute hyperglycaemic rats.
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PMID:Catalase and alpha-tocopherol attenuate blood-brain barrier breakdown in pentylenetetrazole-induced epileptic seizures in acute hyperglycaemic rats. 1184 25

Acute neurodegeneration in man is encountered during and following stroke, transient cardiac arrest, brain trauma, insulin-induced hypoglycemia and status epilepticus. All these severe clinical conditions are characterized by neuronal calcium overload, aberrant cell signaling, generation of free radicals and elevation of cellular free fatty acids, conditions that favor activation of the mitochondrial permeability transition pore (mtPTP). Cyclosporin A (CsA) and its analog N-methyl-valine-4-cyclosporin A (MeValCsA) are potent blockers of the mtPTP and protect against neuronal death following excitotoxicity and oxygen glucose deprivation. Also, CsA and MeValCsA diminish cell death following cerebral ischemia, trauma, and hypoglycemia. Here we present data that strongly imply the mtPT in acute neurodegeneration in vivo. Compounds that readily pass the blood-brain-barrier (BBB) and block the mtPT may be neuroprotective in stroke.
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PMID:Mitochondrial permeability transition in acute neurodegeneration. 1202 55


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