Masayuki Kunimoto

Relationships between benzodiazepine receptors, impairment of GABAergic transmission and convulsant activity of β-CCM: a PET study in the baboon Papio papio

Central type benzodiazepine receptors were studied in vivo by positron emission tomography in brain areas of 2 different groups of the baboon Papio papio: non-photosensitive (group 1) and those with an allylglycine-induced decrease in GABA-mediated inhibition (group 2). Further, a naturally photosensitive Papio papio (+3 level of photosensitive response) was compared to both groups. Regional brain binding of the specific benzodiazepine receptor ligand, [11C]Ro 15-1788, was not significantly different between groups 1 and 2. In addition, the data from the naturally photosensitive Papio papio did not seem to differ markedly from groups 1 and 2 either. Pharmacological effects of increasing doses of beta-CCM (0.05-3 mg/kg i.v.) and regional benzodiazepine receptor occupancy by the drug were simultaneously studied using electroencephalographic activity recording and positron emission tomography. A positive correlation was observed between the degree of photosensitivity of the baboon and sensitivity to the action of beta-CCM, with increasing convulsant efficacy of beta-CCM in going from group 1 to the naturally photosensitive baboon, then to group 2. Dose-related displacement curves of [11C]Ro 15-1788 binding by beta-CCM revealed that reduction in brain GABA concentration did not modify the inhibitory potency of beta-CCM on [11C]Ro 15-1788 binding in cerebral cortex. This suggests a lack of detectable in vivo allosteric effects of GABA on beta-CCM binding during beta-CCM-induced seizures. Thus, a given dose of beta-CCM displayed increasing pharmacological potency in going from baboons with the lowest photosensitivity to those with the highest, whereas benzodiazepine receptor occupancy by beta-CCM was similar in the cerebral cortex of the different baboons. Conversely, a given level of convulsant activity of beta-CCM was related to a different benzodiazepine receptor occupancy by the drug, depending on the photosensitivity of Papio papio. A given dose of a drug may, thus, have a different pharmacological potency when occupying the same number of receptors, depending on the physiopathological state of the subject.

Correlation of EEG, neuroimaging and histopathology in an epilepsy patient with diffuse cortical dysplasia

Abstract The correlation between scalp EEG, intraoperative electrocorticogram, neuroimaging and histopathology was examined in an epileptic child with diffuse cortical dysplasia. The 6-year-old girl with moderate mental retardation had suffered from intractable complex partial and generalized epilepsies since the age of 2 years. MR images demonstrated unilateral large macrogyria/polymicrogyria and schizencephaly in the right occipital lobe. The epileptic focus was detected on the macrogyria by EEG and single photon emission tomography. However, the intraoperative electrocorticogram showed frequent spikes from the polymicrogyria and no paroxysmal activity in the macrogyria. The polymicrogyria and the macrogyric lesion were resected, using an image-guided system. The histological findings revealed that the macrogyria was covered with and separated by glial bundles. It has been reported that epileptogenicity is produced from abnormal neurons and their arrangement in cortical dysplasia; in this case, however, the major dysplastic lesion had no epileptogenicity; rather the focus might be in the polymicrogyria around the lesion.

Antiepileptic effect of nefiracetam on kainic acid-induced limbic seizure in rats

Nefiracetam is being studied as a novel cognition-enhancing agent; however, it has been suggested from studying its chemical structure that it has a potential anticonvulsive effect. We examined the antiepileptic effect of nefiracetam on kainic acid (KA)-induced seizures. KA was infused into the left basolateral amygdaloid nucleus and focal limbic seizures were induced in 43 male Wistar rats. During status epilepticus, 10, 50, 100 or 200 mg/kg of nefiracetam was intravenously injected. Nefiracetam inhibited KA-induced limbic seizures at doses over 100 mg/kg while it had a sedative effect on the animals. In (14C) deoxyglucose autoradiographic studies, the propagation of seizure-induced hypermetabolic areas was also suppressed dose-dependently. From the results, it was indicated that nefiracetam has an antiepileptic effect and that its application may suppress seizure propagation. Further study is required, whether this agent is available as a novel anticonvulsant.

Generalized Tonic Seizures Induced by a Unilateral Microinjection of Kainic Acid into the Pontine Reticular Formation in Rats

Purpose: Following Penfield and Jaspers proposal of the centrencephalic theory, the brainstem reticular formation was believed to be involved in the expression of generalized seizures and the generalization of partial seizures. In our study, an experimental animal model of generalized tonic seizures was produced by the unilateral microinjection of kainic acid (KA) into the pontine reticular formation (PRF) of Wistar rats. In addition, local cerebral glucose utilization (LCGU) was measured during the acute phase of the seizure by autoradiography by using [14C]2‐deoxyglucose to determine the extent of the hypermetabolic area in the brain induced by the seizure.

Ibotenic Acid‐Induced Lesions of Substantia Innominata on Focal Limbic Seizures in Chronic Cats

Eight adult cats were used in this study. Under pentobarbital anesthesia, the cats were stereotaxically operated on and bipolar electrodes were placed in the left amygdala and hippocampus. A Teflon needle for KA microinjection was also implanted into the left amygdala. The detailed techniques were described el~ewhere.~ Moreover, 2.5 pg of ibotenic acid (IBO, 2.5 pg of IBO in 1 pl of a phosphate buffer solution, pH 7.4) was injected into the bilateral SI in 5 cats (Group A) and 1 pl of a phosphate buffer solution in 3 cats (Group B). All the animals were given freedom for at least 8 days to recover from the operation. Then, they were placed in a recording chamber followed by clinical observations and EEG monitoring. One microgram of the KA solution was injected into the amygdala via the implanted Teflon needle. Electroclinical observations were irregularly continued. All the cats were perfused with a 10% formalin solution at the end of each experiment under deep pentobarbital anesthesia and processed for a light microscopic study. Results

Unilateral Diffuse Cortical Dysplasia: A Case Report

Purpose: A case of unilateral diffuse cortical dysplasia is presented, and the surgical strategy is discussed.

Relationship between sleep-wakefulness cycle and regional cerebral blood flow in kainic acid-induced epileptic focus in hippocampus.

Concurrent monitorings of polygraph and continuous measurements of rCBF of the epileptic focus were made in the nonanes‐thetized chronic cats. The influences of the sleep‐wakefulness cycle on IIDs and rCBF of the epileptic focus of the hippocampus were analyzed.

Acute Effect of Potassium Penicillin G on Experimental Focal Epilepsy

Intraperitoneal PC injections could produce secondarily generalized seizures in both the experimental models of focal epilepsy: amygdaloid kindling models and KA‐in‐duced limbic seizure models. In the controls, a large amount of PC induced bilateral cortical epileptiform discharges but not in the limbic structures. The epileptic foci induced by the KA injection are more sensitive to PC than the foci induced by kindling.