The competitive NMDA receptor antagonist CGP 40116 protects against status epilepticus-induced neuronal damage

Fujikawa, Denson G.; Daniels, Allan H.; Kim, John S.

doi:10.1016/0920-1211(94)90051-5

Cited by 98 publications

(85 citation statements)

References 31 publications

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“…This finding confirmed the reports of other laboratories using different animal models. The NMDA receptor antagonist MK 801 administered prior to or shortly after the onset of seizures, did not control kainate-induced or lithium/pilocarpine-induced status epilepticus (Fariello et al, 1989;Walton and Treiman, 1991;Clifford et al, 1990;Fujikawa et al, 1994;Rice and DeLorenzo, 1998). While some authors reported that seizures were less intense after administration of an NMDA receptor antagonist (Rice and DeLorenzo, 1998), others reported that these drugs worsened electrographic seizures (Fariello et al, 1989;Bertram and Lothman, 1990).…”

Section: Discussionmentioning

confidence: 98%

“…Patients dying during or shortly after an episode of status epilepticus show loss of CA1 pyramidal neurons, Purkinje cells of the cerebellum and cortical neurons (DeGiorgio et al, 1992). In the animal models of kainic acid and lithium/pilocarpineinduced status epilepticus the non-competitive NMDA receptor antagonists ketamine, phencyclidine and MK-801 were demonstrated to protect against neuronal damage (Clifford et al, 1990;Fujikawa et al, 1994;Wasterlain et al, 1993). EEG recording from the cortex and hippocampus of an animal subjected to continuous hippocampal stimulation.…”

Section: Discussionmentioning

confidence: 99%

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Ketamine controls prolonged status epilepticus

2000

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New treatments are needed to control prolonged status epilepticus given the high failure rate of current therapies. In an animal model of status epilepticus based on electrical stimulation of the hippocampus, rats demonstrate at least 5 five-hours of seizure activity following stimulation. Phenobarbital (70 mg/kg) administered 15 min after stimulation effectively controlled seizures in 66% of animals (n = 6). When phenobarbital (70 mg/kg) was administered 60 min after stimulation, seizures were controlled in 25% of animals (n = 4). Ketamine (100 mg/kg) administered 15 min after stimulation did not control seizures in any animal (n = 4). But when ketamine was administered one hour after stimulation it effectively controlled seizures in all animals (n = 4). Increasing doses of ketamine were administered 60 min after stimulation to generate a dose-response curve. The ketamine dose response (fraction of seizure free rats) data were fit to a sigmoid curve to derive an ED 50 of 58 mg/kg. These findings suggest that prolonged status epilepticus becomes refractory to phenobarbital but can be effectively controlled by ketamine. For patients experiencing prolonged status epilepticus that is refractory to phenobarbital, ketamine may be an alternative to general anesthesia.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Ketamine controls prolonged status epilepticus

2000

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“…N-Methyl-Daspartate blockers were also shown to be potent protective agents against neuronal loss caused by cholinergic seizures. 12 The standard treatment for organophosphates intoxication consists of pretreatment with pyridostigmine, a reversible inhibitor of AChE and anticholinergic agents such as atropine sulfate. 13 In addition, it was reported that benactyzine (combined with anticholinergic and anti-NMDA properties), or benzodiazepines, could reduce some of the brain damage if administered early enough.…”

Section: Introductionmentioning

confidence: 99%

Blood Glutamate Scavenging as a Novel Neuroprotective Treatment for Paraoxon Intoxication

Ruban

Jona

Teichberg

2013

J Cereb Blood Flow Metab

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Organophosphate-induced brain damage is an irreversible neuronal injury, likely because there is no pharmacological treatment to prevent or block secondary damage processes. The presence of free glutamate (Glu) in the brain has a substantial role in the propagation and maintenance of organophosphate-induced seizures, thus contributing to the secondary brain damage. This report describes for the first time the ability of blood glutamate scavengers (BGS) oxaloacetic acid in combination with glutamate oxaloacetate transaminase to reduce the neuronal damage in an animal model of paraoxon (PO) intoxication. Our method causes a rapid decrease of blood Glu levels and creates a gradient that leads to the efflux of the excess brain Glu into the blood, thus reducing neurotoxicity. We demonstrated that BGS treatment significantly prevented the peripheral benzodiazepine receptor (PBR) density elevation, after PO exposure. Furthermore, we showed that BGS was able to rescue neurons in the piriform cortex of the treated rats. In conclusion, these results suggest that treatment with BGS has a neuroprotective effect in the PO intoxication. This is the first time that this approach is used in PO intoxication and it may be of high clinical significance for the future treatment of the secondary neurologic damage post organophosphates exposure.

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“…A ativação do receptor colinérgico muscarínico (Persinger et al, 1993;Marinho et al, 1998) foi sugerida como responsável pelas convulsões produzidas pela pilocarpina, dando a entender que após ativação do sistema colinérgico haveria uma interação direta e/ou indireta com outros sistemas, a saber: dopaminérgico (Al-Tajir et al, 1990a;Barone et al, 1991), glutamatérgico (Fujikawa et al, 1994(Fujikawa et al, e 1995 e GABAérgico (Fritschy et al, 1999;Erakovic et al, 2000;CostaLotufo et al, 2002), que podem ser ativados para a manutenção e/ou propagação das convulsões. Contudo, os neurotransmissores e as estruturas cerebrais envolvidas na convulsão precisam ser prontamente esclarecidos, a fim de contribuir para a compreensão da gênese do estado epiléptico, bem como investigar novos agentes terapêuticos.…”

Section: Introductionunclassified

Níveis dos neurotransmissores estriatais durante o estado epiléptico

Freitas¹,

Viana²,

Fonteles³

2003

Rev. psiquiatr. clín.

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RESUMOO objetivo desse estudo foi verificar os níveis dos neurotransmissores estriatais de ratas adultas durante o estado epiléptico induzido pela pilocarpina. Ratas wistar foram tratadas com uma única dose de pilocarpina (400 mg/kg por via subcutânea (S.C.); P400) e os controles receberam salina. A concentração dos neurotransmissores foi determinada através do HPLC eletroquímico, no corpo estriado de ratas que no período de observação de 1 hora desencadearam estado epiléptico e que sobreviveram à fase aguda do quadro convulsivo. Foi observada redução nos níveis de dopamina, serotonina, ácido diidroxifenilacético e aumento na concentração do ácido 5-hidroxiindolacético. Nenhuma alteração foi observada no 4-hidroxi-3-metoxi-fenilacético. Os resultados sugerem que a ativação do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo no corpo estriado de ratos desenvolvidos.Unitermos: Dopamina; Serotonina; Convulsão; Corpo estriado. ABSTRACT Striatal monoamines levels during status epilepticusThe purpose of the present work to investigate the striatal neurotransmissors level in adult rats after status epilepticus induced by pilocarpine. Wistar rats were treated with a single dose of pilocarpine (400 mg/kg; s.c.; P400) and the controls received saline. Adult animals were closed observed for behavioural changes during 1h. In this period, the animals that developed status epilepticus and survive this acute phase of seizures had the brains removed and striatal neurotransmissors level determiden by HPLC. The concentration of dopamine, serotonine, dihydroxyphenylacetic acid was reduced and an concentration increase in 5-hydroxyindolacetic acid. Didn't observed alteration in 4-hydroxy-3-methoxy-phenylacetic acid. These results suggest that cholinergic activation can interage with dopaminergic and serotonergic systems in acute phase of the convulsive process in rat mature striatum.

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The competitive NMDA receptor antagonist CGP 40116 protects against status epilepticus-induced neuronal damage

Cited by 98 publications

References 31 publications

Ketamine controls prolonged status epilepticus

Ketamine controls prolonged status epilepticus

Blood Glutamate Scavenging as a Novel Neuroprotective Treatment for Paraoxon Intoxication

Níveis dos neurotransmissores estriatais durante o estado epiléptico

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