Anticonvulsant Properties of Propofol and Thiopentone: Comparison Using Two Tests in Laboratory Mice

Lowson, Stuart M.; Gent, J P; Goodchild, Colin S

doi:10.1093/bja/64.1.59

Cited by 89 publications

(48 citation statements)

References 4 publications

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“…8). There is conflicting data in the literature concerning proconvulsant (DeFriez and Wong, 1992;Cochran et al, 1996) versus anticonvulsant effect of propofol (Lowson et al, 1990;De Riu et al, 1992). Indeed, adverse effects of propofol have been observed in man at induction of anesthesia and its termination before awaking, indicating that the proconvulsant effect of propofol occurs at low blood concentrations (Smith et al, 1996).…”

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confidence: 99%

Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene

et al. 2002

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Four genes encode electroneutral, Na+-independent, K-Cl cotransporters. KCC2, is exclusively expressed in neurons where it is thought to drive intracellular Cl- to low concentrations and shift the reversal potential for Cl- conductances such as GABA(A) or glycine receptor channels, thus participating in the postnatal development of inhibitory mechanisms in the brain. Indeed, expression of the cotransporter is low at birth and increases postnatally, at a time when the intracellular Cl- concentration in neurons decreases and gamma-aminobutyric acid switches its effect from excitatory to inhibitory. To assert the significance of KCC2 in neuronal function, we disrupted the mouse gene encoding this neuronal-specific K-Cl cotransporter. We demonstrate that animals deficient in KCC2 exhibit frequent generalized seizures and die shortly after birth. We also show upregulation of Fos, the product of the immediate early gene c-fos, and the significant loss of parvalbumin-positive interneurons, both indicative of brain injury. The regions most affected are the hippocampus and temporal and entorhinal cortices. Extracellular field potential measurements in the CA1 hippocampus exhibited hyperexcitability. Application of picrotoxin, a blocker of the GABA(A) receptor, further increased hyperexcitability in homozygous hippocampal sections. Pharmacological treatment of pups showed that diazepam relieved the seizures while phenytoin prevented them between postnatal ages P4-P12. Finally, we demonstrate that adult heterozygote animals show increased susceptibility for epileptic seizure and increased resistance to the anticonvulsant effect of propofol. Taken together, these results indicate that KCC2 plays an important role in controlling CNS excitability during both postnatal development and adult life.

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confidence: 99%

Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene

et al. 2002

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“…9~ Experiments carried out in rodents to assess the protection afforded by propofol and thiopentone against induced epileptiform seizures showed that both anaesthetic drugs were effective at sedative doses. 92,93 In an animal model of induced status epilepticus, bolus administration of propofol followed by an infusion completely suppressed electrical and clinical seizures in rabbits. This suggests that propofol may be useful in patients with status epilepticus when other agents have failed.…”

Section: Cerebral Physiology and Metabolismmentioning

confidence: 99%

Propofol in patients with cardiac disease

Searle

Sahab

1993

Can J Anaesth

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“…In rodents, propofol inhibits seizures induced by electroshock, i.v. pentylenetetrazol (Lowson et al, 1990) and i.v. lidocaine (Lee et al, 1998).…”

Section: Sl Peterson Et A! /Neurotoricology 25 (2004) And85-847mentioning

confidence: 99%

Treatment Strategies fir the NMDA Component of Organophosphorous Convulsions

Peterson¹

2005

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and AUTHOR(S)Steven Peterson, Ph.D. The project evaluated anticonvulsant and neuroprotectant properties of novel medical countermeasures to lithium-pilocarpine-induced status epilepticus (SE)used here as a model of organophosphorus nerve agents. Although mefenamate induced modest anticonvulsant effects, survival was reduced and the SE-induced neuropathology was exacerbated. Nicotinamide induced only modest anticonvulsant and neuroprotectant activity at the doses tested. N-acetylcysteine was not anticonvulsant but enhanced both neurological deficit and neuropathology. PBN, but not S-PBN, induced significant neuroprotection. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)8ACPC induced neuroprotection in temporal regions without anticonvulsant activity. D-cycloserine had no effect.Propofol induced significant neuroprotection and anticonvulsant activity in the rat model tested. It is recommended that PBN and ACPC be tested in multiple dose regimens for long term neuroprotetion in nerve agent SE. INTRODUCTIONThis project tested novel treatment strategies for the N-methyl-D-aspartic acid (NMDA) component of organophosphorous (OP) nerve agents that are intended to complement or improve current treatments. OP agents induce an initial cholinergic receptor over stimulation that is followed by a glutamatergic over stimulation of NMDA receptors. The excessive NMDA activation and excitotoxicity results in the status epilepticus (SE), neurological deficit and neuropathology associated with OP intoxication. The lithium-pilocarpine (Li-pilo) model of cholinergic convulsions in rats is used as the experimental model of OP nerve agent-induced SE. The project tests neuroprotectants that protect the brain from seizure-induced neuropathology by interfering with NMDA receptor-mediated intracellular excitotoxicity mechanisms. Experimental parameters used in these studies to assess the test drug activity were: 1) electrocorticograph (ECoG) determination of continuous high amplitude spiking as a measure of SE duration; 2) spontaneous activity before and after SE as a measure of neurological deficit; 3) neuropathology in brain regions damaged by Li-pilo SE.The candidate medical countermeasures tested in the last 12 months of the project were mefenamate, nicotinamide and N-acetylcysteine. The results of those studies are presented in detail. The results of the oc-phenyl-N-tert-butylnitrone (PBN) study are provided in the Appendix in manuscript form (App...

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Anticonvulsant Properties of Propofol and Thiopentone: Comparison Using Two Tests in Laboratory Mice

Cited by 89 publications

References 4 publications

Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene

Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene

Propofol in patients with cardiac disease

Treatment Strategies fir the NMDA Component of Organophosphorous Convulsions

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