Toshinobu Fukushima

Carbamazepine-induced blockade of induction of long-term potentiation in the perforant path-dentate gyrus pathway in chronically prepared rabbits

We investigated the effects of a representative anti-epileptic or anti-psychotic drug, carbamazepine (CBZ), on the induction of long-term potentiation (LTP) in the perforant path-dentate gyrus pathway in 15 chronically prepared rabbits. Pharmacokinetically injected low-dose CBZ, which produced steady serum levels of 2.2-3.3 micrograms/ml (mean +/- S.D. 2.85 +/- 0.40), variably affected the induction of LTP, blocking it or showing almost no effect. The high-dose CBZ, which produced steady serum levels of 6.5-8.6 micrograms/ml (8.01 +/- 0.87), always blocked the induction of LTP. These results indicate that CBZ dose-dependently blocks the induction of LTP. The possible mechanisms underlying this blockade are discussed, especially in association with the possible inhibitory action of CBZ on N-methyl-D-aspartate (NMDA) receptors.

Utility of 123I-IMP SPECT Brain Scans for the Early Detection of Site-Specific Abnormalities in Creutzf eldt-Jakob Disease (Heidenhain Type): A Case Study

Serial changes in brain imaging of regional cerebral blood flow with single photon emission computed tomography (SPECT) using N-isopropyl-(iodine-123) p-iodoamphetamine (123I-IMP) were observed in a patient with probable Heidenhain type of Creutzfeldt-Jakob disease, which was characterized by the initial onset of visual symptoms. Corresponding to the visual signs and periodic synchronous discharges localized in the bilateral parietal and occipital regions on EEG, focal hypoperfusion images in the occipital lobes were detected on the SPECT scan before brain X-ray computed tomography and magnetic resonance imaging showed any abnormalities. These results suggest that SPECT brain imaging is useful in the early detection of site-specific abnormalities in Creutzfeldt-Jakob disease.

Comparison of benzodiazepine receptor and regional cerebral blood floq imaging of epileptiform foci in hippocampal kindled rabbits: a study with in vivo double tracer autoradiography using 125I-Iomazenil and 99mTc-HMPAO

To clarify experimentally whether benzodiazepine (Bz) receptor or regional cerebral blood flow (rCBF) imaging is more sensitive in the detection of epileptic foci, we simultaneously examined the Bz receptor and rCBF distribution changes in hippocampal kindled rabbits with in vivo double tracer autoradiography using 125I-labeled Ro 16-0154 (125I-Iomazenil) and 99mTc-labeled hexamethylpropylene amine oxime (99mTc-HMPAO). In visual and quantitative analyses, 125I-Iomazenil accumulation in brain slices extracted after the completion of the kindling was markedly and extensively decreased in the kindled right CA1 region, and further in the right temporal lobe, dentate gyrus, CA2, CA4, and bilateral CA3 regions, regarded as the propagated sites of seizure discharges. 99mTc-HMPAO accumulation was much more slightly and less extensively decreased in the right CA1, frontal, temporal and dentate gyri. Further, this decrease in 125I-Iomazenil accumulation was not due to neuropathological abnormalities, which consisted only of tissue damage corresponding to electrode track in the CA1. Both the kindled and propagated sites are known to have a possibility of acquiring epileptogenesis as experimental epileptic foci. These results suggest that Bz receptor imaging is much more sensitive in the detection of epileptic foci than rCBF imaging, and therefore that Bz receptor imaging is useful in clinical epilepsy.

Antagonizing correlation between periodic synchronous discharges and photically induced giant evoked responses in Creutzfeldt--Jakob disease (Heidenhain type): a case study.

Abstract In a patient with Creutzfeldt‐Jakob disease (Heidenhain type), which was characterized by the initial onset of visual symptoms and proved by autopsy, there was an antagonizing correlation between spontaneously‐induced periodic synchronous discharges and photically induced giant evoked responses. In addition, the two electroencephalogram features appeared and disappeared in parallel with each other during the clinical course of the illness.

Correlations between quantitative EEG and regional cerebral blood flow (SPECT) in patients with partial epilepsy

During interictal periods in 9 patients with partial epilepsy we examined whether there were correlations between the relative power of background EEG (power spectral analysis) and the absolute values of regional cerebral blood flow (rCBF) measured by 99mTc hexamethylpropylene amine oxime (HMPAO) SPECT in each cerebral region. None of the patients had any organic cerebral lesions on X-ray CT examinations, neurological abnormalities or mental retardation. There was an inverse correlation between rCBF and the relative power of the theta band, and a direct correlation between rCBF and that of the alpha band of 10-12.8 Hz, in the right and/or left frontal, parietal and temporal regions. In the occipital regions, there was a direct correlation only between rCBF and the relative power of the beta band. These correlations were noted whether the analyzed regions were epileptic foci or not. These results suggest that background EEG and rCBF changes in epileptic patients are closely coupled.

Case Study of Monosymptomatic Delusion of Unpleasant Body Odor with Structural Frontal Abnormality

We report a 63-year-old man with a monosymptomatic delusion of unpleasant body odor contracted at the age of 61 years, who believed that his body reeked of some type of paint. He had symmetrical atrophy in the bilateral frontal lobes of unknown etiology on MRI. Further, quantitative rCBF measurement with SPECT brain scan using 99mTc-HMPAO showed relative hypoperfusion localized in the bilateral frontal lobes. EEG, neurological and neuropsychological tests were all normal, including the WAIS-R and Wechsler Memory Scale tests. However, he showed poor results on the Wisconsin Card Sorting test, presumably on account of frontal dysfunction, attaining only two categories with frequent perseverative errors. Although it is undetermined whether the illness in this case can be classified as organic delusional syndrome or paranoid disorder according to DSM-III-R criteria, these results imply that delusions are associated with frontal lobe abnormality.

Comparison of benzodiazepine receptor and regional cerebral blood flow imaging of epileptiform foci in hippocampal kindled rabbits: A preliminary report

To clarify experimentally which of benzodiazepine (BZ) receptor or regional cerebral blood flow (rCBF) imaging is more sensitive in the detection of epileptic foci, we simultaneously examined the BZ receptor and rCBF distribution changes in hippocampal kindled rabbits with in vivo double tracer autoradiography using 125I-labeled Ro 16-0154 (125I-Iomazenil) and 99mTc-labeled hexamethyl-propyleneamine oxime (99mTc-HMPAO). In visual analysis of brain slices extracted after the intravenous injection of the double tracer following the kindling completion, 125I-Iomazenil accumulation was more markedly and extensively decreased in the kindled right CA1 region mimicking a primary epileptic focus than 99mTc-HMPAO accumulation. Further, this decrease in 125I-Iomazenil accumulation was not due to neuropathological abnormalities which consisted only of tissue damage corresponding to electrode track in the right CA1. These results suggest that BZ receptor imaging is more sensitive in the detection of epileptic foci than rCBF imaging and, therefore, that BZ receptor imaging is useful in clinical epilepsy.

Bicuculline-induced blockade of neocortical rapid kindling suggesting facilitative GABAergic action on seizure development.

SummaryTo investigate how GABAergic function affects seizure development, the effects of a GABA antagonist, bicuculline, on neocortical and hippocampal kindling were examined in chronically prepared rabbits. Kindling-inducing stimulations consisted of stimulus trains repeated at 5-min interstimulus intervals to produce so-called “rapid kindling”. The changes in after-discharge (AD) durations induced by each of 15 trials of stimulus trains per session were compared before and 30 min after i.p. injection of bicuculline solution (2 mg/kg) in each of three kindling groups consisting of 5 rabbits each, i.e. visual cortical, motor cortical and hippocampal kindling groups. In the visual cortex and to a less extent, the motor cortex kindling groups, the AD durations were shortened after bicuculline injection and did not show the progressive prolongation seen before the injection. In contrast, the hippocampal kindling group showed a further marked prolongation of the AD durations after the injection. The bicuculline-induced blockade of neocortical kindling suggests facilitative GABAergic action on seizure development, while the drug-induced enhancement of hippocampal kindling reflects the known inhibitory GABAergic action.

Paradoxical GABAergic Facilitation on Seizure Development Observed from Bicuculline‐Induced Effects on Visual Cortical Kindling at Short Interstimulus Intervals in Chronically Prepared Rabbits

Abstract: To investigate the influence of GABAergic function on seizure development, the effects of bicuculline, a GABAa receptor antagonist, on visual cortical and hippocampal kindling were examined in chronically prepared rabbits. Kindling‐inducing stimulations were repeated at 5‐min intervals. The changes in afterdischarge (AD) durations were compared before and 30 min after a low (2 mg/kg) and high dose (5 mg/kg) i.p. injection of bicuculline solution. In the visual cortical kindling group, the AD durations were markedly shortened after the low dose bicuculline injection, while bicuculline produced a prolongation of the AD durations in the visual cortical with the high dose injection and hippocampal kindling groups. The low dose bicuculline‐induced inhibition of visual cortical kindling suggests facilitative GABAergic action on seizure development, while the drug‐induced enhancement in the other groups reflects the well‐known inhibitory GABAergic action.