Glucose utilization in the brain during acute seizure is a useful biomarker for the evaluation of anticonvulsants: effect of methyl ethyl ketone in lithium-pilocarpine status epilepticus rats.
Enhancement of glucose utilization in the brain has been well known during acute seizure in various kinds of animal model of epilepsy. This enhancement of glucose utilization might be related to neural damage in these animal models. Recently, we found that methyl ethyl ketone (MEK) had both anticonvulsive and neuroprotective effects in lithium-pilocapine (Li-pilo) status epilepticus (SE) rat. In this article, we measured the uptake of [(14)C]2-deoxyglucose ([(14)C]DG) in the Li-pilo SE and Li-pilo SE with MEK rat brain in order to assess whether the glucose utilization was a useful biomarker for the detection of efficacy of anticonvulsive compounds. Significant increase of [(14)C]DG uptake (45 min after the injection) in the cerebral cortex, hippocampus, amygdala and thalamus during acute seizure induced by Li-pilo were observed. On the other hand, the initial uptake of [(14)C]DG (1 min after the injection) in the Li-pilo SE rats was not different from the control rats. Therefore, the enhancement of glucose metabolism during acute seizure was due to the facilitation of the rate of phosphorylation process of [(14)C]DG in the brain. Pretreatment with MEK (8 mmol/kg) completely abolished the enhancement of glucose utilization in the Li-pilo SE rats. The present results indicated that glucose utilization in the brain during acute seizure might be a useful biomarker for the evaluation of efficacy of anticonvulsive compounds.
Yamada
Akifumi
A
Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan. yamaaki@sahs.med.osaka-u.ac.jp
Momosaki
Sotaro
S
Hosoi
Rie
R
Abe
Kohji
K
Yamaguchi
Masatoshi
M
Inoue
Osamu
O
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002074:Butanones / Q000008:administration & dosage*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D018021:Lithium Chloride; D008297:Male; D010862:Pilocarpine; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D015415:Biomarkers; D002074:Butanones; D010862:Pilocarpine; C005222:methylethyl ketone; D018021:Lithium Chloride; D005947:Glucose