Anticonvulsant properties of acetone, a brain ketone elevated by the ketogenic diet
The ketogenic diet (KD), a treatment for drug‐resistant epilepsy, elevates brain acetone. Acetone has been shown to suppress experimental seizures. Whether elevation of acetone is the basis of the anticonvulsant effects of the KD and whether acetone, like the KD, antagonizes many different types of...
Saved in:
Published in | Annals of neurology Vol. 54; no. 2; pp. 219 - 226 |
---|---|
Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.08.2003
Willey-Liss |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | The ketogenic diet (KD), a treatment for drug‐resistant epilepsy, elevates brain acetone. Acetone has been shown to suppress experimental seizures. Whether elevation of acetone is the basis of the anticonvulsant effects of the KD and whether acetone, like the KD, antagonizes many different types of seizures, however, is unknown. This study investigated the spectrum of the anticonvulsant effects of acetone in animal seizure models. Rats were injected with acetone intraperitoneally. Dose–response effects were measured in four different models: (1) the maximal electroshock test, which models human tonic‐clonic seizures; (2) the subcutaneous pentylenetetrazole test, which models human typical absence seizures; (3) the amygdala kindling test, which models human complex partial seizures with secondary generalization; and (4) the AY‐9944 test, which models chronic atypical absence seizures, a component of the Lennox–Gastaut syndrome. Acetone suppressed seizures in all of the models, with the following ED50's (expressed in mmol/kg): maximal electroshock, 6.6; pentylenetetrazole, 9.7; generalized kindled seizures, 13.1; focal kindled seizures, 26.5; AY‐9944, 4.0. Acetone appears to have a broad spectrum of anticonvulsant effects. These effects parallel the effects of the KD. Elevation of brain acetone therefore may account for the efficacy of the KD in intractable epilepsy. Ann Neurol 2003 |
---|---|
Bibliography: | NSERC - No. CHRP238016-00 Savoy Foundation istex:66D8AE871AAEAE4CCBF66FE772478D434187B7B4 ArticleID:ANA10634 Bloorview Children's Hospital Foundation - No. 00024256 The Canadian Institutes of Health Research - No. 14329MOP Hospital for Sick Children Pediatric Consultants - No. 77710-62300 ark:/67375/WNG-RPD02LDQ-T |
ISSN: | 0364-5134 1531-8249 |
DOI: | 10.1002/ana.10634 |