title: Methyl ethyl ketone blocks status epilepticus induced by lithium-pilocarpine in rats.
abstract: OBJECTIVE
  A ketogenic diet has been used successfully to treat patients with intractable epilepsy, although the mechanism is unknown. Acetone has been shown to have an anticonvulsive effect in various animal models. The main purpose of this study was to determine whether other ketones, 2-butanone (methyl ethyl ketone: MEK) and 3-pentanone (diethyl ketone: DEK), also show anticonvulsive effects in lithium-pilocarpine (Li-pilocarpine)-induced status epilepticus (SE) in rats.
  
  
  METHODS
  Anticonvulsive effects of MEK and DEK in Li-pilocarpine SE rats were measured by behavioural scoring. Anti-seizure effects of MEK were also evaluated using electroencephalography (EEG). Neuroprotective effect of MEK was investigated by haematoxylin and eosin staining 4 weeks after the treatment with pilocarpine.
  
  
  RESULTS
  Acetone, MEK and DEK showed anticonvulsant effects in Li-pilocarpine-induced SE rats. Treatment with MEK twice (8 mmol.kg(-1) and 5 mmol.kg(-1)) almost completely blocked spontaneous recurrent cortical seizure EEG up to 4 weeks after the administration of pilocarpine. MEK also showed strong neuroprotective effects in Li-pilocarpine-treated rats 4 weeks following the administration of pilocarpine. Significant neural cell death occurred in the hippocampus of Li-pilocarpine SE rats, especially in the CA1 and CA3 subfields. In contrast, normal histological characteristics were observed in these regions in the MEK-pretreated rats.
  
  
  CONCLUSIONS
  Both MEK and DEK showed strong anticonvulsive effects in Li-pilocarpine-induced SE rats. They also inhibited continuous recurrent seizure and neural damage in hippocampal region for 4 weeks after the treatment with pilocarpine. These findings appear to be of value in the investigation of epilepsy.
authors.affiliation: Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka, Japan. inoue@sahs.med.osaka-u.ac.jp
authors.forename: Osamu
authors.initials: O
authors.lastname: Inoue
authors.forename: Eriko
authors.initials: E
authors.lastname: Sugiyama
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hasebe
authors.forename: Noriko
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Rie
authors.initials: R
authors.lastname: Hosoi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Kohji
authors.initials: K
authors.lastname: Abe
authors.forename: Antony
authors.initials: A
authors.lastname: Gee
mesh_terms: D000096:Acetone / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002074:Butanones / Q000627:therapeutic use*; D055423:Diet, Ketogenic; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D018021:Lithium Chloride; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010422:Pentanones / Q000627:therapeutic use; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000927:Anticonvulsants; D002074:Butanones; D018696:Neuroprotective Agents; D010422:Pentanones; D010862:Pilocarpine; D000096:Acetone; C005222:methylethyl ketone; C027452:diethyl ketone; D018021:Lithium Chloride
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