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

In the lithium-pilocarpine model (Li-pilocarpine) of temporal lobe epilepsy, GABA(A) receptor-mediated inhibitory postsynaptic currents (GABA(A) IPSCs) were recorded in dentate gyrus granule cells (GCs) from adult rat hippocampal slices. The properties of GABA(A) IPSCs were compared before and after superfusion of modulators in control conditions (Li-saline rats) and in Li-pilocarpine rats 24-48 h and 3-5 months (epileptic rats) after status epilepticus (SE). The mean peak amplitude of GABA(A) IPSCs increased by about 40% over Li-saline values in GCs 24-48 h after SE and remained higher in epileptic rats. In Li-pilocarpine rats, studied at 24-48 h after SE, diazepam (1 microm) lost 65% of its effectiveness at increasing the half-decay time (T(50%)) of GABA(A) miniature IPSCs (mIPSCs). Diazepam had no effects on mIPSC T(50%) in epileptic rats. The benzodiazepine ligand flumazenil (1 microm), acting as an antagonist in Li-saline rats, exhibited a potent inverse agonistic effect on GABA(A) mIPSCs of GCs from Li-pilocarpine rats 24-48 h and 3-5 months after SE. The neurosteroid allopregnanolone (100 nm), which considerably prolonged GABA(A) mIPSCs in Li-saline rats, totally lost its effect in rats studied 24-48 h after SE. However, this decrease in effectiveness was transient and was totally restored in epileptic rats. In addition to the up-regulation in the number of receptors at individual GC synapses, we propose that these 'epileptic' GABA(A) receptors possess benzodiazepine binding sites with altered allosteric properties. The failure of benzodiazepine and neurosteroid to potentiate inhibition early after SE may be a critical factor in the development of epileptogenesis and occurrence of seizures.
 ...
PMID:Pharmacological plasticity of GABA(A) receptors at dentate gyrus synapses in a rat model of temporal lobe epilepsy. 1503 26

Catalase is one of the enzymes that convert hydrogen peroxide (H2O2) to H2O presenting a protective role against free radicals. In this study, catalase activity was determined in homogenates of striatum (ST) and prefrontal cortex (PFC) in order to examine the participation of oxidative stress (OS) on cocaine actions in mice brain. Male Swiss mice were injected (i.p.) with cocaine at low (10 and 30 mg/kg) and high doses (90 mg/kg), and observed for 1 h. After cocaine overdose (90 mg/kg) some animals presented only status epilepticus (SE) while others died after seizures. These animals were dissected and divided in two groups, SE and death. Catalase activity was also determined after pretreatment with the anticonvulsant drug, diazepam, alone or injected before cocaine 90 mg/kg, and after seizures induced by a high dose of bupropion, a known inhibitor of NE and DA reuptake used for comparison. Results showed a decrease in catalase activity of the PFC and ST after SE and death induced by cocaine and bupropion overdoses. Cocaine at low doses decreased the enzyme activity only in ST. Diazepam treatment alone and before cocaine overdose did not interfere with catalase activity. This reduction in catalase activity may reflect an increase in H2O2 content in PFC and ST. Previous data reports that H2O2 inhibits dopamine transporter activity, suggesting that the decrease in catalase activity may potentiate the toxic mechanism of drugs that inhibit monoamines reuptake. As far as we know, this is the first report showing an involvement of OS in the cocaine's central mechanism of action.
 ...
PMID:Cocaine alters catalase activity in prefrontal cortex and striatum of mice. 1608 63

We investigated the sequence of the administration, the efficacy and the safety of antiepileptic drugs (AED) given intravenously for the treatment of status epilepticus and frequent seizures in children. Our institute has a recommended sequence of AED administration for treatment of status epilepticus: the first-line agent is diazepam (0.3 - 0.5 mg/kg administered intravenously, once or twice). The second-line drugs include midazolam (0.15 - 0.4 mg/kg intravenously, once or twice, and if necessary, followed by continuous infusion at 0.06 - 0.18 mg/kg/hour), lidocaine (1 - 2 mg/kg intravenously, once or twice, and if necessary, followed by continuous infusion at 2 - 4 mg/kg/hour) and phenytoin (10 - 20 mg/kg, infused slowly). For those patients who previously experienced a seizure which was refractory to diazepam but responsive to the second-line agent, it was recommended to use the second-line agent as a first-line agent. When seizures were refractory to the first and second-line agents, thiopental was administered (3 - 10 mg/kg intravenously, and if necessary, followed by continuous infusion at 2 -5 mg/kg/hour). The etiologies of 177 occasions of status epilepticus and frequent seizures were categorized into two groups:epilepsy (n = 95) and situation-related seizures (n = 82). Situation-related seizures included febrile seizures (n = 44), acute encephalopathy/encephalitis (n = 31) and benign infantile convulsions (n = 7). The ages of the patients ranged from 0.1 to 18.4 years (average +/- SD:3.69 +/- 3.15 years). Diazepam was administered as the first-line drug on 157 of 177 occasions (88.7%). On 116 occasions the second-line agents were administered. Midazolam and lidocaine were injected as the second-line agent on 54 (46.6%), and on 33 (28.4%) occasions, respectively, although both midazolam and lidocaine injections were off-label use for seizure control in Japan. Thiopental was used as the third to fifth-line agent. Effective ratios (effective occasions/total occasions) of each drug were the following: thiopental 19/21 (90.4%), midazolam 57/99 (57.6%), lidocaine 25/60 (41.7%), phenytoin 16/41 (39.0%), diazepam 59/164 (36.0%). Thiopental was statistically more effective than midazolam, lidocaine, diazepam or phenytoin (p < 0.01), and midazolam was statistically more effective than diazepam (p < 0.01) or phenytoin (p < 0.05). Administration of thiopental caused complications more frequently than the other agents (p < 0.01): The complications by thiopental were severe in some cases requiring intratracheal intubations and artificial ventilation. From the viewpoint of both efficacy and safety, midazolam should be recommended as one of the first-line agents for status epilepticus.
 ...
PMID:[Choice and administration sequence of antiepileptic agents for status epilepticus and frequent seizures in children]. 1616 45

We studied the effects of treating status epilepticus (SE) induced by lithium and pilocarpine at postnatal day 15 (P15) or 28 (P28), on the severity of acute SE and of SE-induced epileptogenesis. Rats received topiramate (10 or 50 mg/kg, IP) or diazepam (5 mg/kg, IP) 20, 40 or 70 min after pilocarpine, and three months after SE 24-h video/EEG recordings were obtained for one (P28) or two weeks (P15) continuously. In P15 rats, topiramate did not modify the course of SE, yet treatment at 20 or 40 min completely prevented the development of spontaneous recurrent seizures (SRS) while later treatment (70 min) was partially effective in reducing the severity and frequency of SRS. Diazepam was effective against acute SE at all time points tested. Early (20 min) but not late treatment with diazepam had the effect of reducing the frequency and severity of SRS. In P28 rats, both drugs reduced the cumulative seizure time. Early treatment (20 min) with either drug reduced the incidence of chronic epilepsy. Late treatment (40/70 min) did not alter the incidence of SRS, but decreased their frequency. This study demonstrates that, in the treatment of SE, anticonvulsant and antiepileptogenic effects can be dissociated in a development-specific manner: topiramate was antiepileptogenic without being an effective anticonvulsant in P15 animals at the doses tested. Diazepam, on the other hand, was a better anticonvulsant than an antiepileptogenic agent in the P15 animals at the dose tested. Such effects were not seen in the older animals.
 ...
PMID:Treatment of experimental status epilepticus in immature rats: dissociation between anticonvulsant and antiepileptogenic effects. 1726 49

Organophosphate (OP)-nerve agent poisoning may lead to prolonged epileptiform seizure activity, which can result in irreversible neuronal brain damage. A timely and effective control of seizures with pharmacological agents can minimize the secondary and long-term neuropathology that may result from this damage. Diazepam, the current anticonvulsant of choice in the management of OP poisoning, is associated with unwanted effects such as sedation, amnesia, cardio-respiratory depression, anticonvulsant tolerance, and dependence liabilities. In search for an efficacious and safer anticonvulsant benzodiazepine, we studied imidazenil, a potent anticonvulsant that is devoid of sedative action and has a low intrinsic efficacy at alpha1- but is a high efficacy positive allosteric modulator at alpha5-containing GABA(A) receptors. We compared the potency of a combination of 2 mg/kg, i.p. atropine with: (a) imidazenil 0.05-0.5 mg/kg i.p. or (b) equipotent anti-bicuculline doses of diazepam (0.5-5 mg/kg, i.p.), against diisopropyl fluorophosphate (DFP; 1.5 mg/kg, s.c.)-induced status epilepticus and its associated neuronal damage. The severity and frequency of seizure activities were determined by continuous radio telemetry recordings while the extent of neuronal damage and neuronal degeneration were assessed using the TUNEL-based cleaved DNA end-labeling technique or neuron-specific nuclear protein (NeuN)-immunolabeling and Fluoro-Jade B (FJB) staining, respectively. We report here that the combination of atropine and imidazenil is at least 10-fold more potent and longer lasting than the combination with diazepam at protecting rats from DFP-induced seizures and the associated neuronal damage or ongoing degeneration in the anterior cingulate cortex, CA1 hippocampus, and dentate gyrus. While 0.5 mg/kg imidazenil effectively attenuated DFP-induced neuronal damage and the ongoing neuronal degeneration in the anterior cingulate cortex, dentate gyrus, and CA1 hippocampus, 5 mg/kg or a higher dose of diazepam is required to produce similar protective effects. These finding suggests that imidazenil, a non-sedating anticonvulsant BZ ligand, is a more potent, effective, and safer drug than diazepam in protecting rats from DFP-induced seizures and the associated neuronal damage and/or ongoing neuronal degeneration.
 ...
PMID:Imidazenil, a non-sedating anticonvulsant benzodiazepine, is more potent than diazepam in protecting against DFP-induced seizures and neuronal damage. 1911 86

Functional alterations in movement representations (motor maps) have been observed in some people with epilepsy and, under experimental control, electrically-kindled seizures in rats also result in persistently larger motor maps. To determine if a single event of status epilepticus and its latent consequences can affect motor map expression, we assessed forelimb motor maps in rats using the pilocarpine model of temporal lobe epilepsy. We examined both pilocarpine-induced seizures, and status epilepticus (SE) in two strains that differ in their propensity for epileptogenesis; Wistar and Long-Evans. Pilocarpine was administered intraperitoneally at dosages that resulted in equivalent proportions of seizures, SE, and survival in both strains. Rats from both strains were given saline injections as a control. Diazepam was administered to all rats to attenuate seizure activity and promote survival. All rats had high-resolution movement representations derived using standard intracortical microstimulation methodologies at 48 h, 1 week, or 3 weeks following treatment. Pilocarpine-induced seizures only gave rise to motor map enlargement in Wistar rats, which also showed interictal spiking, and only at 3 weeks post-treatment indicating altered motor map expression in this strain following a latent or maturational period. Pilocarpine-induced SE yielded larger motor maps at all time points in Wistar rats but only a transient (48 h) map expansion in Long-Evans rats. Our results demonstrate that seizures and SE induced by a convulsant agent alter the functional expression of motor maps that is dependent on seizure severity and a genetic (strain) predisposition to develop epileptiform events.
 ...
PMID:Motor map expansion in the pilocarpine model of temporal lobe epilepsy is dependent on seizure severity and rat strain. 1936 1

In principle, the use of anticonvulsant drugs does not differ between acute and remote symptomatic seizures, but control of acute symptomatic seizures requires simultaneous treatment of the underlying etiology. Prevention of remote seizures when the risk is known to be high has been the subject of intense efforts at antiepileptogenesis, but the optimal duration of treatment after an injury is not yet known. Appropriate evaluation of a seizure depends on individual circumstances, but findings on examination, laboratory tests (serum electrolytes, magnesium, glucose, assessment of hepatic and renal function), and brain imaging (CT scan or MRI) are necessary to determine the most likely cause. Lumbar puncture is always required when there is suspicion of meningitis or encephalitis. Preferred medications for treatment of acute symptomatic seizures or status epilepticus are those available for intravenous use, such as benzodiazepines, fosphenytoin or phenytoin, valproate, levetiracetam, and phenobarbital. Diazepam is also available as a gel for rectal administration. Seizures that occur in patients with epilepsy because of missed antiepileptic drugs or inadequate serum levels should be treated with additional doses of their regular medications; loading doses can be administered with minimal toxicity in tolerant patients. Surgery is rarely necessary in the acute setting except for intracerebral lesions with rapidly rising intracranial pressure and impending herniation. After seizures are controlled, the provoking condition must also be determined and treated.
 ...
PMID:Treatment of acute and remote symptomatic seizures. 1952 49

In the present study the effectiveness of different diazepam-ketamine combinations to control kainic acid-induced status epilepticus in rats was evaluated. We show that electrographic monitoring is mandatory to enable reliable assessment of status epilepticus control as the number of false positives is extremely high when status epilepticus control is only behaviourally assessed. Diazepam and ketamine synergistically blocked all electrographical seizure activity.
 ...
PMID:The control of kainic acid-induced status epilepticus. 2043 12

Status epilepticus of the generalized tonic-clonic form is a serious, life-threatening neurological emergency. Management must be swift and effective to protect the brain from anoxic damage and serious neurological sequelae. Most cases are due to withdrawal or non-compliance with anticonvulsant medication in known epileptics. Diazepam, phenytoin and phenobartital are effective in stopping these episodes. Other drugs may be effective in certain individuals, but most appear to work with `hit or miss' effectiveness. Barbiturate anesthesia is an effective method of ending status epilepticus episodes when the primary agents have failed, and this step should be undertaken early in the management of resistant cases.
 ...
PMID:Status epilepticus: a plan for management. 2128 3

Aim of this review was to evaluate efficacy and safety of intravenous valproate (IV VPA) in the treatment of generalized convulsive status epilepticus (GCSE) in patients of any age, synthesizing available evidences from randomized controlled trials (RCTs). RCTs on IV VPA administered in patients (no age restriction) for GCSE at any stage were searched in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials. Studies were selected and data independently extracted. Following outcomes were considered: clinical seizure cessation after drug administration, seizure freedom at 24 h, and adverse effects. Outcomes were assessed using standard methods to calculate risk ratio (RR) with 95% confidence intervals. Five trials met inclusion criteria. Two different comparisons were available (IV VPA versus phenytoin (PHT), IV VPA versus IV Diazepam), but only the former included more than one study with enough information to permit a meta-analysis. Compared with PHT, VPA had statistically lower risk of adverse effects (RR 0.31, 95% CI 0.12-0.85), with no differences in GCSE cessation after drug administration (RR 1.31, 95% CI 0.93-1.84) and in seizure freedom at 24 h (RR 0.96, 95% CI 0.88-1.06). This review suggests that IV VPA has a better tolerability than PHT in treatment of GCSE, without any statistically significant differences in terms of efficacy. More rigorous RCTs of VPA versus an appropriate comparator, in a well-defined population with a systematic definition of SE, are however required to conclude about efficacy and tolerability of VPA in clinical practice.
 ...
PMID:IV Valproate in generalized convulsive status epilepticus: a systematic review. 2218 4


<< Previous 1 2 3 4 5 6 7 Next >>