Hideo Mabe

Effect of Nimodipine on Cerebral Functional and Metabolic Recovery Following Ischemia in the Rat Brain

Whether the calcium entry blocker, nimodipine, prevents the increase in the concentration of free fatty acids and metabolic disturbances during ischemia and promotes functional and metabolic recovery after recirculation were examined. Severe forebrain ischemia in rats was induced by four-vessel occlusion with mild hypotension. After 30 minutes of ischemia, recirculation was started by removal of the arterial clamps and by increasing blood pressure to the preischemic level. Recovery of EEG activity following recirculation was better in the nimodipine-treated group than in the control group. During the ischemic period, there were no significant differences in accumulation of free fatty acids or in depletion of ATP between treated and control groups. At 120 minutes following recirculation, recovery of the ATP level was significantly better in the treated group than in the control group. Therefore, the promotion of functional and metabolic recovery by nimodipine-treatment is suggested to be not due to the prevention of an accumulation of free fatty acids nor to the depletion of ATP during the ischemic period, but to either improvement of postischemic hypoperfusion or a direct action on metabolic processes during reperfusion period.

Improvement of passive avoidance task after grafting of fetal striatal cell suspensions in ischemic striatum in the rat

Behavioral recovery and cell survival/growth after grafting of fetal striatal cell suspensions in the ischemic striatum of rats were investigated. Ischemia was induced by one hour intraluminal occlusion of the right middle cerebral artery under halothane anesthesia. During the ischemia rats usually manifested signs of hemiparesis and sometimes rotations. Behavioral function was measured by a passive avoidance task and radial arm maze test at 1-2 weeks and 6-7 weeks after ischemia. The size of the ischemic lesions depended on each animal, but the ischemic animals showed deficits in both passive avoidance task and radial maze test. Two weeks after ischemia, fetal striatal cells, marked with DiI, were transplanted into the ischemic striatum. The transplantation improved the ischemia-induced deficit in the passive avoidance task but not in radial maze test. Although there were variations in the size of the grafts, many DiI-positive cells with dendritic outgrowth were detected under fluorescent microscopy. Immunohistochemical study revealed that many choline acetyltransferase (ChAT) positive cells and GABA-positive cells survived in the grafts. However, striosome-matrix compartments were not evident inside the grafts. Thus, partial recoveries in both cytoarchitectural and behavioral aspects were obtained by striatal cell grafts, suggesting that neural transplantation could be a useful approach in reconstructing ischemic brain function.

A phospholipase C inhibitor ameliorates postischemic neuronal damage in rats.

Background and Purpose The hypothesis of calcium-induced neuronal damage has been proposed regarding brain ischemia. Phospholipase C is an enzyme that catalyzes the phosphodiesteratic cleavage of phosphatidylinositol. The cleavage of phosphatidylinositol 4,5-bisphosphate by phospholipase C yields 1,4,5-inositol triphosphate, which mediates intracellular release of calcium, and 1,2-diacylglycerol, which is an activator of protein kinase C. We examined the effect of phenylmethylsulfonyl fluoride, a phospholipase C inhibitor, on delayed neuronal damage after transient forebrain ischemia in the hippocampal CA1 subfield in rats to assess the role of phospholipase C in postischemic neuronal damage. Methods Twenty-minute forebrain ischemia was induced using the method of Pulsinelli and Brierley. We measured the neuronal density of the hippocampal CA1 subfield 7 days after reperfusion. The effect of phenylmethylsulfonyl fluoride was tested in both pretreatment and posttreatment groups. Results In the vehicle treatment group (n = 13), neuronal density was 51±42/mm (mean±SD). The neuronal densities in the 50-mg/kg (n=12) and 100-mg/kg (n=14) phenylmethylsulfonyl fluoride pretreatment groups and the 100-mg/kg (n=10) phenylmethylsulfonyl fluoride posttreatment group were 99 ±50, 150 ±55, and 143±63/mm, respectively. These values were significantly higher than that of the vehicle treatment group (p<0.05, p<0.01, and p<0.01, respectively). Conclusions It is suggested that the activation of phospholipase C has an important role in postischemic delayed neuronal damage.

Serum neuron-specific enolase levels after subarachnoid hemorrhage

We examined serum levels of neuron-specific enolase by enzyme immunoassay in 29 patients with subarachnoid hemorrhage due to ruptured cerebral aneurysm. Serum neuron-specific enolase levels were significantly higher in patients with a poor neurological status than in patients with a good neurological status on admission, and the greater the amount of subarachnoid blood, the higher the serum neuron-specific enolase level. Patients with a good outcome had low serum neuron-specific enolase levels throughout their courses. Serum neuron-specific enolase levels increased with development of delayed ischemic neurological deficits and, especially in poor outcome patients, high levels persisted until 3 weeks after the subarachnoid hemorrhage.

Role of brain tissue leukotriene in brain oedema following cerebral ischaemia: effect of a 5-lipoxygenase inhibitor, AA-861.

It has been postulated that lipoxygenase metabolites of arachidonic acid play a role in the pathogenesis of cerebral ischaemia. Severe forebrain ischaemia in rats was induced by four-vessel occlusion with mild hypotension. After 30 min of ischaemia, circulation was restored by removing the arterial clamps and increasing blood pressure to preischaemic levels. During 30 min of cerebral ischaemia, free arachidonic acid increased by approximately 8.5 times compared with the preischaemic level. This accumulation was reversed within 60 min of reperfusion. The concentration of leukotriene C4 in brain tissue increased significantly during reperfusion: treatment with a 5-lipoxygenase inhibitor, AA-861, decreased the increase of brain water content associated with reperfusion. This study demonstrated that the increased arachidonic acid resulting from cerebral ischaemia in rats is metabolized to leukotrienes via the lipoxygenase pathway once circulation is restored, and these leukotrienes may play some role in the development of postischaemic cerebral oedema.

A typical moyamoya disease associated with brain tumor

A 4-year-old boy with right retinal hemorrhage, mental retardation, and multiple minor anomalies was referred to our hospital. Computed tomography scanning revealed a cystic brain tumor at the vermis. Angiography showed stenosis of both internal carotid arteries at the supraclinoid portion and the Moyamoya vessels. The right ophthalmic artery was dilated as wide as the internal carotid artery. Stenosis of the basilar artery was also observed. Collateral circulation via the posterior inferior cerebellar artery and Moyamoya vessels in the area of the posterior cerebral artery was observed.

Cerebral blood flow after ventriculoperitoneal shunt in children with hydrocephalus

Fourteen hydrocephalic children were studied who were between the ages of 6 months and 14 years. Regional cerebral blood flow (rCBF) was measured by the 133Xe intravenous injection method after ventriculoperitonal shunting. There was a negative correlation between slow flow and preoperative ventricular size (r=-0.718, P<0.02), but there was no correlation between fast flow and preoperative ventricular size. There was also no correlation between rCBF and postoperative ventricular size. Postoperative IQ or development quotient showed a positive correlation with slow flow (r=0.813, P<0.01), but not with fast flow. It is suggested that in hydrocephalic children there is impairment of white-matter communicating fibres and secondary reduction in higher intellectual activity.

Production of Platelet-Activating Factor During Focal Cerebral Ischemia and Reperfusion in the Rat

Platelet-activating factor (PAF) is a phospholipid mediator implicated in a diverse range of pathological processes. Beneficial effects of PAF antagonists have been shown in various models of central nervous system ischemia. In this study, we evaluated the production of PAF during focal cerebral ischemia and reperfusion in the rat. Ischemia was induced by occlusion of the middle cerebral artery with a thread. Quantification of PAF was performed with the radioimmunoassay technique. PAF was detected in the brain under normal conditions. Tissue PAF level in the ischemic cerebral hemisphere significantly decreased by prolonged ischemia (P<.05). Conversely, the decreased tissue PAF level during ischemia was significantly increased again by reperfusion (P<.05), but was still low compared with the control. This study indicates that the production of PAF in the brain tissue decreased by prolonged ischemia, and suggests the role of PAF in the reperfusion phase rather than during ischemia in the pathophysiology of ischemic brain injury.

Changes in epidural pulse pressure in brain oedema following experimental focal ischaemia.

This study was carried out to clarify the changes of pulse pressure of the intracranial pressure pulse wave in ischaemic brain oedema. Intracranial pressure and PP were measured in two groups of anaesthetized dogs; 1) increased volume of cerebrospinal fluid by cisternal saline injection (control group), 2) brain oedema caused by focal ischaemia (oedema group). Ischaemia was induced by 2 hours of occlusion of the anterior, middle cerebral and internal carotid arteries. The canine focal ischaemic model showed consistent ischaemic damage in the caudate nucleus and produced brain oedema successfully. PP increased linearly with rising ICP to 35 mm Hg, and PP in the oedema group was significantly smaller than that in the control group at the same ICP value. The slopes of the regression equation of ICP and PP were significantly different between the oedema and control group (oedema: 0.057 +/- 0.029, control: 0.106 +/- 0.009), mean +/- SD, P less than 0.005). These results suggest that PP is easily affected by ischaemic brain oedema, which indicates increase of the brain tissue in the cranium. We conclude that PP is affected even at the same ICP value when intracranial components have altered.

Regional Cerebral Blood Flow after V-P Shunt in Hydrocephalic Children

There have been few reports about cerebral blood flow in children with hydrocephalus. We measured rCBF by the 133Xe intravenous injection method after ventriculoperitoneal (V-P) shunt in 14 hydrocephalic children between ages of 6 months and 14 years.