Kazuhiro Sako

Cerebral blood flow and histopathological changes following permanent bilateral carotid artery ligation in Wistar rats

SummaryCerebral blood flow and histopathological changes after bilateral carotid artery ligation (BCAL) in Wistar rats were studied. Eight of the 38 rats (21%) died within one week. In the 30 survivors, the incidence of histopathological change was 90% in the caudate nucleus, 23% in the cortex, 30% in the hippocampus, and 0% in the other structures. Local cerebral blood flow (LCBF) was measured using the quantitative autoradiographic 14C-iodoantipyrine technique in 24 anatomically discrete regions of the brain. BCAL induced ischemia in the entire forebrain. The percent reduction of LCBF was between 25–94% of the control at 2.5 h after BCAL. LCBF tended to recover 1 week after BCAL except for the regions of neuronal damage. These results suggest that neuronal damage does not correlate with the flow rate. In the present study, selective neuronal damage was also observed in rats with chronic cerebral ischemia.

Local cerebral glucose utilisation following acute and chronic bilateral carotid artery ligation in Wistar rats: relation to changes in local cerebral blood flow.

The effects on local cerebral blood flow (LCBF) and glucose utilisation (LCGU) of permanent, bilateral carotid artery ligation (BCAL) were studied in conscious Wistar rats. LCBF and LCGU were measured using quantitative autoradiographic 14C-iodoantipyrine and the 14C-2-deoxyglucose (14C-DG) techniques in 24 anatomically discrete regions of the brain. LCBF in the cerebral hemispheres 2.5 h (acute) after BCAL significantly decreased to 25–87% of the sham control, with the exception of the mammillary body. After acute BCAL, there was a heterogeneous accumulation of 14C-DG in the caudate nucleus and cerebral cortices. Only in the lateral geniculate body did LCGU significantly decrease after BCAL. One week (chronic) later, LCBF was significantly decreased in 15 (containing the caudate nucleus and all the cerebral cortices) of 24 structures. LCGU in ten (containing the caudate nucleus and all the cerebral cortices) of 24 structures after chronic BCAL significantly decreased to 66–77% of the sham control, except for regions with neuronal damage in which there was a heterogeneous uptake of 14C-DG. The ratio of LCBF/ LCGU in chronic BCAL was unchanged in comparison with values in the corresponding sham-operated group. This model of acute and chronic cerebral ischaemia, with impairment in cerebral circulation and/or glucose metabolism, is expected to become a pertinent tool for the neurophysiologist.

Uncoupling of local blood flow and metabolism in the hippocampal CA3 in kainic acid-induced limbic seizure status

Limbic seizure status was induced by microinjection of kainic acid into a unilateral amygdala in rats. Two hours after kainic acid injection, distant neuronal cell damage was produced, especially in the hippocampal CA3 on the kainic acid-injected side. In order to elucidate the mechanism of this neuronal cell damage, local cerebral glucose utilization and local cerebral blood flow were studied by means of an autoradiographic method using [14C]2-deoxyglucose and [14C]iodoantipyrine during kainic acid-induced limbic seizure status. These studies were performed 2 h after kainic acid microinjection into a unilateral amygdala. Both local cerebral glucose utilization and local cerebral blood flow were remarkably increased in the limbic system, ventrobasal complex of the thalamus, septal nucleus, nucleus accumbens, caudate nucleus, substantia nigra and hypothalamus on the kainic acid-injected side. In the hippocampus, local cerebral glucose utilization increased 2.6 times control in CA1 and 4.1 times in CA3, whereas the rates of increase in local cerebral blood flow were similarly low in CA1 and CA3: 1.2 and 1.4 times control, respectively. The results demonstrated that the degree of uncoupling of local cerebral glucose utilization and local cerebral blood flow were higher in CA3 than in CA1, and also suggested that relative hypoxia occurred in CA3 in this high degree of uncoupling, resulting in pyramidal cell damage in CA3 in kainic acid-induced limbic seizure status.

Diagnosis and treatment of progressive space-occupying radiation necrosis following stereotactic radiosurgery for brain metastasis: Value of proton magnetic resonance spectroscopy

Summary¶Background. There have been some reports that radiation necrosis can be controlled conservatively. There are rare cases showing progressive space-occupying radiation necrosis (PSORN). It is very difficult to control PSORN by conservative treatment. The purpose of this study was to evaluate the early diagnosis of those cases and the timing of surgery for patients with PSORN.Method. We have experienced some cases where quality of life was improved by the removal of PSORN after stereotactic radiosurgery (SRS) for brain metastases. Therefore, we evaluated retrospectively the diagnosis and treatment of six cases of symptomatic PSORN at approximately 6–12 months after SRS for metastatic brain tumours.Findings. In all six cases, on Magnetic Resonance Imaging with Gd contrast material (Gd-MRI), PSORN was revealed as a ring-like enhanced mass with large perifocal oedema coupled with the appearance of neurological deficit. Proton Magnetic Resonance Spectroscopy (1H-MRS) enabled us to differentiate PSORN from recurrence of metastases in all six cases. Single Photon Emission Computed Tomography with thallium-201 chloride (201TlCl-SPECT) enabled us to do this in four cases of the six. In four cases of the six, lesionectomy of the ring-like enhanced mass (PSORN) was performed, and in two of these cases the removal was performed within 4 weeks from the time when conservative treatment became ineffective, and the neurological deficit and perifocal oedema was improved as was the quality of life. However, in the other two patients who were left for more than 16 weeks, the deficit was gradually progressive. The two patients who did not receive lesionectomy were treated by conservative means with steroids and/or heparin and warfarin and they had progressive neurological symptoms.Interpretation. Although, the number of patients is small in this study, and more data will be needed, it is recommended that lesionectomy is performed at an early stage, if possible, when conservative management has failed.

Regional calcium accumulation and kainic acid (KA)-induced limbic seizure status in rats

The sites of calcium accumulation were studied by 45Ca autoradiography during kainic acid (KA)-induced limbic seizure in rats. Two hours after KA injection into unilateral amygdala, calcium accumulated in CA3 of the hippocampus, lateral septal nucleus and thalamic reticular nucleus on KA-injected side. Those sites coincided with the sites where neuronal cell damage appeared 4 h after KA injection. These results suggested that regional calcium accumulation might be responsible for neuronal cell loss induced by seizures.

Hypothermia attenuates hyperglycolysis in the periphery of ischemic core in rat brain.

Abstract Hypothermia has proven to be neuroprotective against ischemic brain injury. However, the exact mechanism has not yet been fully understood. In this study, we investigated the effects of hypothermia on cerebral glucose metabolism and blood flow in focal ischemic rats. Rats were divided into normothermic (37±0.5°C) and hypothermic (30±0.5°C) groups. Focal cerebral ischemia was induced by middle cerebral and ipsilateral common carotid arteries occlusion. Two hours after ischemia, autoradiographic studies of 2-deoxyglucose and iodoantipyrine were performed to measure local cerebral glucose utilization (LCGU) and cerebral blood flow. LCGU in the ischemic core was excessively reduced in both groups. However, a marked increase in LCGU was observed in the boundary zone of the ischemic core in normothermic rats. On the other hand, hyperglycolysis in the boundary zone of the ischemic core was suppressed in hypothermia. This attenuation of hyperglycolysis might be closely related to survival of the ischemic penumbra in hypothermia.

Consecutive in vivo measurement of nitric oxide in transient forebrain ischemic rat under normothermia and hypothermia

The effects of hypothermia on production of nitric oxide (NO) in ischemic brain were investigated by using in vivo microdialysis. Male Wistar rats were randomly divided into three groups; saline-treated normothermic group (37 degreesC, n=6), 30 mg/kg N-nitro-l-arginine methyl ester(l-NAME)-treated normothermic group (n=6), and saline-treated hypothermic group (30 degreesC, n=6). Transient forebrain ischemia was produced by bilateral common carotid artery occlusion combined with hypotension (MABP=50 mmHg). Saline-treated normothermic animals resulted in a reduction of LCBF to 9% of baseline. Saline-treated hypothermic rats revealed the similar changes of LCBF. In contrast, l-NAME administration reduced the basal CBF to 85% of saline-treated group and to 8% after ischemia. NO products were decreased during ischemia and transiently increased after reperfusion in saline-treated groups. However, the increase of NO products after reperfusion was less significant in the hypothermia. l-NAME-treated group showed a constant reduction of NO production during ischemia and after reperfusion.

The effects of HA1077, a novel protein kinase inhibitor, on reductions of cerebral blood flow and glucose metabolism following acute and/or chronic bilateral carotid artery ligation in Wistar rats

The effects of HA1077, a novel protein kinase inhibitor on local cerebral blood flow (LCBF) 2.5 h (acute) after permanent bilateral carotid artery ligation (BCAL) and on LCBF and local cerebral glucose utilisation (LCGU) one week (chronic) after BCAL were studied in conscious Wistar rats. Use was made of quantitative autoradiographic 14C-iodoantipyrine and the 14C-2-deoxyglucose techniques and 24 anatomically discrete regions of the brain. HA1077 (1 or 3 mg/kg) or saline was infused i.v. over a 30 min period. HA1077 significantly increased LCBF after acute BCAL in one of the 23 decreased regions in rats given 1 mg/kg, and in 14 of 23 decreased regions in rats given 3 mg/kg, compared to findings in the saline-treated group. Significant increases in LCBF and LCGU after chronic BCAL were noted in seven of the 13 decreased regions and in four of the 11 decreased regions in rats given 3 mg/kg, as compared to observations in the corresponding saline-treated group, respectively. The LCBF and LCGU reductions in forebrain regions with global ischaemia after acute and/or chronic BCAL were overcome by HA1077. These results suggest that HA1077 may be considered for treatment of subjects with acute and chronic cerebral ischaemia, with impairment in cerebral circulation and/or glucose metabolism.

HA1077, a novel calcium antagonistic antivasospasm drug, increases both cerebral blood flow and glucose metabolism in conscious rats

The effects of a novel calcium antagonistic antivasospasm drug, HA1077, on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were studied in 33 anatomically discrete regions of the brain in conscious rats, using the quantitative autoradiographic [14C]iodoantipyrine and [14C]2-deoxyglucose techniques. HA1077 was infused i.v. over a 30-min period (1 or 3 mg/kg). HA1077 significantly increased LCBF in 9 of 33 sites in rats given 1 mg/kg, and in 14 of 33 sites in rats given 3 mg/kg compared to the control group given vehicle. Significant increases in LCGU were also noted in 16 of 33 sites in rats given 3 mg/kg. HA1077 increased both cerebral blood flow and glucose metabolism in conscious rats.

Coarctation of the descending aorta with aneurysm of the anterior communicating artery

A case of a 19-year-old woman who had coarctation of the descending aorta associated with an aneurysm of the anterior communicating artery is reported. The aneurysm was successfully clipped during the acute phase of subarachnoid hemorrhage.