Methyl ethyl ketone blocks status epilepticus induced by lithium-pilocarpine in rats.
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.
Inoue
Osamu
O
Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka, Japan. inoue@sahs.med.osaka-u.ac.jp
Sugiyama
Eriko
E
Hasebe
Nobuyoshi
N
Tsuchiya
Noriko
N
Hosoi
Rie
R
Yamaguchi
Masatoshi
M
Abe
Kohji
K
Gee
Antony
A
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
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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