lithium-chloride and methylethyl-ketone

Significant increases in local cerebral blood flow during lithium-pilocarpine (Li-P) induced seizure have been reported. We recently found that both acetone and methyl ethyl ketone (MEK) showed anticonvulsive effects in status epilepticus induced by Li-P in rats. In this study, we examined whether MEK also suppressed the enhancement of local cerebral blood flow induced by Li-P with a simplified autoradiographic method using [(14)C]-para-iodo-N-isopropyl amphetamine ([(14)C]-IMP). Significant increases in local cerebral blood flow in the thalamus, hypothalamus, hippocampus and cerebellum were observed in Li-P induced status epilepticus rats. Pretreatment with MEK (8 mmol/kg) completely suppressed the enhancement of local cerebral blood flow to or below the control level in all regions.

Topics: Animals; Anticonvulsants; Autoradiography; Butanones; Carbon Radioisotopes; Cerebellum; Cerebrovascular Circulation; Hippocampus; Hypothalamus; Iofetamine; Lithium Chloride; Male; Pilocarpine; Rats; Rats, Wistar; Status Epilepticus; Thalamus

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.. 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.. 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.. 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.

Topics: Acetone; Animals; Anticonvulsants; Butanones; Diet, Ketogenic; Hippocampus; Lithium Chloride; Male; Neuroprotective Agents; Pentanones; Pilocarpine; Rats; Rats, Wistar; Status Epilepticus

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.

Topics: Animals; Anticonvulsants; Biomarkers; Brain; Butanones; Drug Evaluation, Preclinical; Epilepsy; Glucose; Lithium Chloride; Male; Pilocarpine; Radionuclide Imaging; Rats; Rats, Wistar