Kazuaki Kawashima

Behavioral, electroencephalographic and histopathological studies on mongolian gerbils with occluded common carotid arteries

The effect of brain ischemia on passive avoidance test was investigated in mongolian gerbils with ischemia induced by a 5 min bilateral occlusion of the carotid arteries. Severe impairment of memory was apparent when the training session of the passive avoidance test was carried out 2 or 14 days after the bilateral ischemia. Two days after the occlusion, the amplitude of hippocampal theta waves were slightly decreased and Nissls degradation was apparent in the CA1 neurons in the hippocampus. The changes in hippocampal neurons become progressively more severe. The amplitude of the hippocampal theta waves diminished considerably and the CA1 neurons in the hippocampus disappeared 14 days after the occlusion. We suggest that the hippocampal damage, especially abnormalities in the CA1 neurons, evidenced by histopathological and electroencephalographic results, may be related to deficits in memory following bilateral common carotid arteries occlusion.

Involvement of amygdaloid catecholaminergic mechanism in suppressive effects of desipramine and imipramine on duration of immobility in rats forced to swim

The suppressive effect of systemic injection of desipramine and imipramine on the duration of immobility in rats forced to swim was inhibited by 6-hydroxydopamine given into the medial amygdaloid nucleus as a pretreatment. Pretreatment with 5,7-dihydroxytryptamine given into the medial amygdaloid nucleus had no effect on the immobility-reducing effect of tricyclic antidepressants. The concentrations of catecholamines and serotonin in 6-hydroxydopamine- and 5,7-dihydroxytryptamine-pretreated rats, respectively, were significantly lower than those in the saline-injected rats. These results suggest that the suppressive effect of systemic injection of desipramine and imipramine on the duration of the immobility of rats forced to swim was mediated by the catecholaminergic but not the serotonergic mechanisms in the medial amygdaloid nucleus.

Prostacyclin analogue TTC-909 reduces memory impairment in rats with cerebral embolism

The effects of the stable prostacyclin analogue TTC-909 on memory impairment in the water maze task and on neuronal damage were studied in rats with cerebral embolism induced by injecting polyvinyl acetate (PVA) into the right internal carotid artery and the ensuing embolism extending out into the right middle cerebral artery. Areas supplied by the lenticulostriate artery were most markedly damaged. In the water maze test, the PVA-embolized rats took longer to reach the platform than did the nontreated control rats. To some extent, repeated administrations of TTC-909 (200 ng/kg, IV) overcame this impairment in water maze learning in the rats. We assume that the vasodilating effects of TTC-909 maintain this blood supply to the ischemic area and that TTC-909 prevents the development of thrombosis around the PVA particles in the arterial capillaries, as a result of antiplatelet aggregative effects. These two mechanisms are likely to be involved in memory improvement. TTC-909 may prove effective for treating subjects with stroke and other cerebrovascular disorders.

Effects of VA-045, a novel apovincaminic acid derivative, on age-related impairment evidence in electroencephalograph, caudate spindle, a passive avoidance task and cerebral blood flow in rats.

1. The ability of VA-045 to improve aged-related impairment on electroencephalograph (EEG), caudate spindle, performance on a passive avoidance task and cerebral blood flow (CBF) were evaluated in rats. 2. The cortical EEG of the aged rats showed a higher incidence of spontaneous spindle burst (SSB) than seen in young rats. VA-045 decreased the incidence of SSB in aged rats. In contrast, vinpocetine increased the incidence of SSB in aged rats. 3. Electrical stimulation of the striatum in aged rats lead to a higher incidence of neocortical high voltage spindle (CS) than seen in young rats. In young rats, VA-045 had no effect on the CS, whereas an age-related increase in CS was blocked by VA-045, but was enhanced by vinpocetine. 4. There were no differences in the cortical EEG arousal response elicited by stimulation of the reticular formation of the brain stem in rats of all ages. VA-045 and vinpocetine had no effect on the cortical EEG arousal response in both young and aged rats. 5. VA-045, but not vinpocetine, attenuated the age-related decreased step through latency (STL) on a passive avoidance task. VA-045 and vinpocetine did not enhance the acquisition of learning behavior in a passive avoidance task in young rats. 6. VA-045 increased the cerebral blood flow (CBF) in both young and aged rats and the potency in aged rats was greater than that in young rats. Vinpocetine had no effect on CBF in either young or aged rats. 7. The pharmacological effects of VA-045 on age-related neuronal dysfunction are discussed.

Amygdaloid catecholaminergic mechanisms involved in suppressive effects of electroconvulsive shock on duration of immobility in rat forced to swim

Chronic but not acute treatment with electroconvulsive shock (ECS) significantly reduced the duration of immobility in rats forced to swim. The immobility-reducing effect of chronic treatment with ECS was strongly antagonized by 6-hydroxydopamine but not by 5,7-dihydroxytryptamine given into the medial amygdaloid nucleus. These results indicate that ECS, like the tricyclic antidepressants, reduces the duration of immobility in rats forced to swim and that catecholaminergic mechanisms in the medial amygdaloid nucleus are involved in the suppressive effect of ECS on the duration of immobility, as are the tricyclic antidepressants.

Protective effects of minaprine in infarction produced by occluding middle cerebral artery in stroke-prone spontaneously hypertensive rats.

1. We examined the effects of minaprine on cerebral infarction produced by occluding of unilateral middle cerebral artery (MCA) above the rhinal fissure in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Oral administration of minaprine (60 mg/kg/day) and vehicle were started 30 min after the occlusion of MCA, and continued for 6 days. 3. The brain was dissected out and 36 coronal multiple sections of the whole brain were histologically prepared to determine the location and extension of infarction. 4. The infarcted area produced by the occlusion of MCA was limited to the cerebral cortex. 5. Body weight of the minaprine-treated rats gradually decreased within 4 days after the occlusion of MCA and thereafter increased, whereas in the vehicle-treated rats, there was a gradual decrease during the experimental period. 6. Size of the infarcted area was serially measured, in each section, using a microcomputer imaging device. In all animals with an occluded MCA, there was a typical pattern of ischemic damage. 7. Post-treatment of MCA occluded SHRSP with minaprine resulted in reduction in infarct size, as compared to findings in the vehicle-treated controls. 8. The pharmacological and histopathological effects of minaprine on the progress of cerebral infarction produced by the occlusion of MCA in SHRSP are discussed.