A new model of cerebral embolism in Wistar rats in which recirculation of the blood flow in ischemic areas can be introduced by means of removal of embolus in an easy way was designed. Large cerebral infarction in the territory of the right middle cerebral artery was induced by the embolization of a silicone rubber cylinder attached to a nylon surgical thread which was positioned at the segment where the right internal carotid artery branches into the middle cerebral artery. Recirculation in the ischemic area was performed successfully by removal of the cylcinder by simply pulling thread out from the artery.
Influence of the recirculation on water contents and histological changes in the brains were investigated. Water contents in the brains increased from 77.62% in controls to 79.48% in the experimental group 12 hours after embolization. Recirculation for 2 hours after the various duration of ischemia enhanced the water contents significantly as compared to the brains receiving embolism for the same duration without recirculation. Reflow of the blood into the infarcted area resulted in increased vascular permeability leading to more severe edematous spongy changes in the brains and extravasation of erythrocytes and granulocytes from the small vessels in the infarcted area.

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It is widely accepted that the autoregulation and chemical regulation of cerebral blood flow are impaired in the acute stage of stroke and that various vasoactive substances are also released in this stage. Therefore, the present study was aimed at investigating whether central endogenous prostaglandins, the potent vasoactive substances, contributed to the regulations of cerebral circulation in the acute stroke.
The study was carried out in 36 patients with acute stroke (within 7 days after the onset; mean ± S.D.=3.6 ± 1.9 days), ranging in age from 45 to 83 (64.8 ± 9.8 yr.) including 17 occlusive and 19 hemorrhagic lesions. Blood samples were taken from the brachial artery and from the internal jugular vein at the level of jugular bulb. Blood gases and pH were measured by using the Corning 168 pH/blood gas analyzer. Cerebral blood flow was estimated by means of the method of arterio-venous oxygen difference. Changes in cerebral perfusion pressure (CPP) were induced by head-up tilt method and changes in PaCO₂ were induced by 7% CO₂ + air inhalation. The cerebral vasomotor responses to changes in perfusion pressure and to changes in PaCO₂ were quantitatively estimated by dysautoregulation index (|ΔCBF/ΔCPP|; %/mmHg) and chemical index (|ΔCBF/ΔPaCO₂|; %/mmHg). Prostaglandins (PG E, PG F_2α & 6-ketoPG F_1α, the stable metabolite of PG I₂) and catecholamines during the steady stage were measured by means of radioimmunoassay and high performance liquid chromatography methods.
The results were summarized as follows :
1) The levels of arterial and cerebral venous PG E had significant correlations with the dysautoregulation index, the degree of cerebral vasomotor response to changes in perfusion pressure (r=0.521·p<0.01, r=0.479·p<0.05, respectively).
2) No significant correlations were obtained between the level of arterial PG E and the chemical index, but the level of cerebral venous PG E had a significant reverse correlation with the chemical index (r=-0.536, p<0.05).
3) The levels of arterial and cerebral venous PG F_2α did not have any significant correlation with either the dysautoregulation index or the chemical index.
4) No significant correlations were observed between the level of arterial 6-keto-PG F_1α and the dysautoregulation index, but the level of cerebral venous 6-keto-PG F_1α had a significant correlation with the dysautoregulation index. (r=0.688, p<0.05).
5) The level of arterial 6-keto-PG F_1α had a significant reverse correlation with the chemical index (r=-0.957, p<0.01), but no significant correlations were observed between the level of cerebral venous 6-keto-PG F_1α and the chemical index.
6) The levels of arterial and cerebral venous noradrenaline did not show any significant correlation with dysautoregulation index, chemical index or the level of PG E.
From the above data, it is suggested that the central endogenous PG E and PG I₂ play important roles in the regulations of cerebral blood flow, cerebral vasomotor responses to changes in perfusion pressure and PaCO₂.

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Cardiac thrombosis has been generally considered to be a major origin of cerebral embolism in Japanese population. With the recent increase of severe atherosclerosis, it was expected that different opinions concerning the source of cerebral embolus might be risen. Is the real source of the emboli just as generally assumed?
With the object of elucidating this problem, macroscopical as well as microscopical investigations were carried out on the hearts, aortas, carotid arteries, cerebral arteries and brains collected from 30 autopsy cases ranging from 43 to 97 years old in age, who died from cerebral embolism in the period from 1978 through 1983.
The results were as follows : A considerable number of arteriogenous emboli (6 in 30) were found besides cardiogenous ones (16 in 30) in Japanese patients with cerebral embolism. This was especially frequent in both advanced aged autopsy and clinically hypertensive cases (p<0.01). It was also detected that many of arteriogenous emboli were derived from thrombosis induced on atherosclerotic lesions.
As ulcer and thrombosis associated with severe atherosclerosis could often become the sources of arteriogenous emboli, total number of their foci were counted in all the present cases. Their frequency distributions were as follow : Many of them were observed not only in the carotid sinus (10), well known in this regard, but also in the proximal brachiocephalic artery (11), ascending aorta and aortic arch (13), the right and left proximal segments of common carotid (7), subclavian (8) and vertebral arteries (1). All these lesions were regarded as important sources of emboli.
Clinicopathologically, the average age of cardiogenous cerebral embolism cases at death was 65 ± 12 years old and that of arteriogenous 76 ± 11. The mean value for the hematocrits in the blood of these embolism cases patients were 44.5% which was higher than that of 70 year-old control (p<0.01).

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A 50-year-old hypertensive man presented the typical dysarthria-clumsy hand syndrome manifested by severe dysarthria, central facial weakness, dysphagia, deviation of the tongue on protrusion, clumsiness, incoordination of the affected hand, and mild imbalance on walking. CT performed on the day of admission revealed a small hematoma in the right upper pons.
After 20 days, CT showed complete resolution and correlated with clinical improvement.
The dysarthria-clumsy hand syndrome is attributed to a lacunar infarct in the pons, internal capsule and corona radiata, but it is an uncommon presentation of primary pontine hemorrhage.

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We investigated the effects of metoprolol, propranolol and phentolamine on hemodynamic conditions, arterial norepinerphrine and epinephrine levels, renin activity, and renal plasma flow in 6 patients with ruptured intracranial aneurysm and 2 patients with hypertensive putaminal hemorrhage suffering from systemic arterial hypertension. Phentolamine was a potent antihypertensive, but increased intracranial pressure. Propranolol, a non-selective β blocker, reduced renal plasma flow. However, metoprolol, a cardioselective β₁ blocker, did not decrease renal plasma flow, but did reduce arterial norepinephrine, epinephrine levels, and renin activity. Moreover, the agent did not influence intracranial pressure and cerebral perfusion pressure. Our findings indicate that metoprolol can be safely used as an antihypertensive drug to control acute systemic arterial hypertension in patients with intracranial mass lesions and/or intracranial hypertension.

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The authers studied 252 cases with subarachnoid hemorrhage due to ruptured intracranial aneurysms, admitted from January 1982 through December 1984. Among these cases, 25 cases died within a short period due to severe angiospasm, and we reported the clinical characteristics of these cases.
These cases were apt to occured in female of sixth and seventh decade. CT on admission showed remarkably high density in all cisterns, and CT at the time of symptomatic angiospasm revealed extensive cerebral infarction in the area of the middle cerebral arterial supply with severe cerebral edema, which accompanied by obvious midline shift. Also, multiple cerebral infarction were seen in the other cases. In the laboratory data on admission, leucocytosis, elevation of blood surger, abnormal changes of ECG and disorders of lipid metabolism were observed. It was suggested that dysfunction of the hypothalamus and cerebral arteriosclerosis attributed to the severe angiospasm. Early operation for ruptured aneurysm and preventive admninstration of calcium antagonist tended to reduce severe angiospasm.

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Clinical profiles of cerebral embolism were studied in relation to the incidence, course and predisposing factors of recurrent attacks in a series of 186 consecutive cases, who were diagnosed as certain cerebral embolism based on our diagnostic criteria reported elswhere. Atrial fibrillation (AF) without valvular heart disease (59 cases) and valvular heart disease (VHD, 58 cases) were the two main underlying cardiac disorders. More than 90% of the remaining 69 cases were found to have various types of heart disease.
Within two weeks prior to the cerebral embolism which caused admission to our hospital, 24 patients (13%) had experienced 27 episodes of cerebral (14 episodes) and/or systemic (13 episodes) embolization, suggesting an importance of minor episodes as a warning sign of major strokes. During the acute stage (Day 1-Day 14), recurrent cerebral embolism were observed in 0.51%/patient-day and systemic embolization in 0.81%/patient-day. A patient-recurrence rate of cerebral embolization during this stage was 7%, and when the systemic embolization was included, the recurrence rate increased to 14%. These incidences were higher than those in the subacute (Day 15-Day 28) and the chronic (Day 29-Day 60) stages. Ninety-one percent of the cerebral and 41% of the systemic recurrence caused an increment of mortality and morbidity.
An incidence of early recurrent embolization to the brain in patients with AF was approximately the same as that in VHD patients, but early systemic episodes ocurred more frequently in VHD than in AF patients. Although the incidence of early systemic and brain recurrences was somewhat different by age and sex, these differences seemed partly to be a reflection of a disparity of underlying cardiac disorders among these groups. Fibrinolytic therapy in the acute stage seemed to increase the recurrence rate by almost 3 times.
Importance of correct diagnosis of embolic stroke and of establishment of secondary preventive measure of early recurrence were emphasized.

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A case of cerebral infarction with massive hyperlipidemia during estrogen-progesterone (E-P compound) therapy was reported. The patient was a 52 year-old female, who had myoma uteri with profuse menstruation (hypermenorrhea) and anemia. One week after she started to take E-P compound for a purpose of altering her menstrual cycle, she suddenly developed dense right hemiplegia and global aphasia.
Computed tomography at the time of admission in Taiwan showed wide-spread hypodense area with scattered hyperdense spots in the territory supplied by the left middle cerebral artery (MCA). Serum triglyceride was markedly increased (2, 264 mg/dl) and lipoprotein analysis in electrophoresis revealed a high population of pre β-lipoprotein.
Despite a presence of large hemispheric infarction, carotid angiography performed on the 25th day revealed occlusion of branches of MCA with retrograde filling of the peripheral portion.
From the clinical profiles and neuroradiological findings, she was diagnosed as cerebral embolism. Although any possible underlying organic disorders that cause cerebral embolization were not detected, a presence of hypercoagulable state shown by thromboelastogram and decreased activity of lipoprotein lipase in heparin test strongly suggested that E-P compound has played a part in the development of cerebral infarction through changing lipid metabolism and coagulation system. The relation between E-P compound and the development of cerebral infarction was discussed.

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Three digit dichotic listening test made by Sugishita and Iwata was performed in six patients with fluent aphasia due to the left hemispheric lesion, and the results obtained were analysed in relation with the recovery of aphasia evaluated by token test.
The laterality index of the dichotic repetition test revealed that the ear dominance is not directly related with the improvement of aphasia. On the other hand, the scores of right ear performance, both by the repetition test and the pointing test by the right hand, showed close correlation with scores of token test, while the left ear performance did not reveal any correlation with the recovery of aphasia. The lesion analysis with CT scan revealed that those in whom both the acoustic radiation and the transverse gyri of the left hemisphere were affected in addition to the lesion of the Wernicke area showed neither recovery from aphasia or improvement of right ear performance in dichotic listening test.
From these results, the recovery from fluent aphasia seems to be assured not by the left-to-right shift of the hemispheric dominance but by the improvement of the language function of the affected hemisphere.

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To investigate the hemodynamics in collateral circulation through the circle of Willis, we studied the changes of large vessel resistance (LVR) and small vessel resistance (SVR) after the occlusion of common carotid arteries (CCAS) using the micropressure system.
Fourteen adult cats anesthetised with alpha-chloralose and urethane were studied under mechanical ventilation. Systemic arterial blood pressure (SAP) and PeCO₂ were monitored. After the partial craniotomy, a pial branch of left middle cerebral artery (100-200 micron of diameter) was punctured with a glass capillary connected to a micropressure recording device. Cerebral blood flow (CBF) was measured by the hydrogen clearance method. LVR was expressed as the pressure difference between SAP and pial arterial pressure (PAP) devided by CBF. The vascular resistance of the circle of Willis was expressed by the increase of LVR after each CCA occlusion. SVR was determined as PAP/CBF.
The PAP decreased from 72 mmHg to 62 mmHg (p<0.001) after the left CCA occlusion, and to 44 mmHg (p<0.001) after bilateral CCAs occlusion. The SAP increased from 117 mmHg to 128 mmHg (p<0.001) after bilateral CCAs occlsion at the first time. The CBF in steady state was 32 ml/100 gm/min, which did not change after the left CCA occlusion, but fell to 24 ml/100 gm/min (p<0.001) after bilateral CCAs occlusion. LVR increased from 1.52 mmHg/ (ml/100 gm/min) to 2.05 (p<0.001) with the left CCA occlusion, then to 3.85 (p<0.001) after bilateral CCAs occlusion. So the resistance of anterior part of the circle of Willis is 0.53 and that of posterior part including vertebrobasilar artery artery is 2.33. SVR in steady state was 2.60 and decreased to 2.28 (p<0.005) with the left CCA occlusion, but did not show further change after bilateral CCAs occlusion. This experimental model seems to be useful in studying dynamics of collateral circulation via the circle of Willis.

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It is generally accepted that the only middle cerebral artery occlusion does not cause permanent tissue damage in the MCA territory in dogs. In this experiment, we occluded the anterior, middle cerebral and internal carotid arteries of one side via transorbital approach. This approach has several advantages as follows. 1) Easy setting of the electrodes on the convexity 2) keeping tightness of the cranium 3) Minimal operative damage. The following parameters were employed. 1) 1-CBF (Hydrogen clearance) 2) EEG : Berg-Fourier analyzer 3) Intracranial pressure (EDP) 4) Clinical symptoms 5) Microcirculation by carbon black injection. All of the survived dogs showed hemiparesis at 24 hours after occlusion of the vessels. L-CBF of the cortex near the Sylvian fissure decreased to about 10 ml/100 g/min. Cortical flow near the sagittal sinus decreased to about 35 ml/100 g/min immediately after occlusion. EEG changes after occlusion was divided into three groups. The first group showed immediate suppression of the electrical activity. The second group revealed transient increase of the slow wave component. The last group did not change EEG markedly except slight reduction of the EEG amplitude. EDP was measured until 6 hours after occlusion. More than 20 mmHg elevation from the control value was observed. Histological examination using microcarbon revealed temporo-occipital ischemic area sparing anterior cerebral artery territory with mild midline shift. The caudate nucleus and thalamus were also involved in this model. This canine focal ischemic model does not need hypotension using exsanguination or other. And also, reduction of the 1-CBF was good enough to observe the ischemic threshold.

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Regional cerebral blood flows (rCBF) of cortex, thalamus and midbrain were measured in dog's brain by the hydrogen inhalation method using hydrogen electrodes. Denervation of cerebral circulation was performed by intracisternal injection of 6-Hydroxydopamine (6-OHDA). Effects of induced hypertension by stenosis of thoracic aorta with a Fogarty balloon catheter and induced hypotension by exsanguination of rCBF were tested in the 3 groups which were 1, 4 and 7 days after denervation groups and non-denervation group. Pressure-flow relationship curves were drawn using the data of each experiment and autoregulation of the regional circulation was checked as to whether or not the curves has a plateau. Findings were as follows :
1. Denervation with 6-OHDA induced slight increasing of rCBF in each region at a steady state, but not statistically significant.
2. In the denervation groups, disappearance of autoregulation first began on brain stem circulation and the autoregulation of cortical circulation remained last. Seven days after denervation, however, disautoregulation was seen in all circulations.
3. Changing rate of cerebrospinal fluid pressure for the change of mean arterial blood pressure (ΔCSF-P/ΔMABP) was calculated in each group. ΔCSF-P/ΔMABP was progressively increased after denervation and it was supposed that vasoparalysis was induced.
With these results, it was certain that denervation by 6-OHDA disappeared the autoregulation of regional cerebral circulation. Effect of the denervation, however, was different on brain stem circulation and on cortical circulation. Then, it was considered that central neural degeneration was induced by 6-OHDA and the disappearance of a myogenic factor was also induced by the degeneration. It may be ascertained that the disappearance of autoregulation of cortical circulation was caused by both degeneration and the disappearance of the myogenic factor.

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