Occlusion of a middle cerebral artery (MCA) with the transorbital approach produces a satisfactory experimental model of focal cerebral ischemia and this method has found widespread application in cats and primates.
With the transorbital approach, the MCA is exposed easily through the enlarged optic foramen, while the integrity of the cranium is maintained and disturbance or manipulation of the brain is avoided. Delayed closure with an implanted device placed around the MCA allows for extended physiological observation of an animal suffering from ischemic cerebral damage.
Since the first description of this model in cat by O'Brien and Waltz in 1973, a considerable amount of research with this model has been reported. In the present paper, literature dealing with transorbital MCA occlusion in cat as an experimental model of focal cerebral ischemia is reviewed, and the usefulness and shortcomings of this model are discussed.

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Since Sundt et al reported a retro-orbital MCA occlusion model, the model has been modified to trans-orbital approach and widely used in the experiments on cerebral ischemia. We modified the model in order to produce cerebral ischemia in awake state with minimum artificial change of intracranial pressure or leakage of CSF, and to be able to recirculate. For implantation of an MCA occlusion device, the MCA was exposed transorbitally and looped with nylon or prolene thread. The free ends of the thread was passed through two small holes of a small polyvinyl plate, placed loosely on the MCA, and then passed within a polypropyrene tube which was anchored to the orbit by dental cement after the craniotomy opening was sealed initially with gelfoam. The skin incision over the orbit was then sutured. Two to seven days after the implantation, the occlusion and recirculation of the MCA by our occlusion device was checked with cerebral angiography and rCBF measurement. Our modification of the MCA occlusion model to approximate clinical situations would be of value for studies on cerebral ischemia.

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Effects of acute and chronic sympathetic denervation on cerebral blood flow and arterial hypertrophy in the parietal cortex were examined in SHR of various age.
At 9 weeks, 4 months, and 6 months, basal mean arterial blood pressure were 115 ± 8, 114 ± 7, and 168 ± 6 mmHg, and upper limits of autoregulation were 149 ± 6, 182 ± 7, and 210 ± 11 mmHg, respectively. In acutely denervated hemisphere, these upper limits were lowered to 132 ± 5, 165 ± 5, and 187 ± 9 mmHg, respectively.
In chronic denervation (ganglionectomy at 4 weeks of age), the upper limits in the denervated hemisphere were also shifted to the lower blood pressure levels; 190 ± 9 in the intact hemisphere and 168 ± 8 mmHg in the denervated one at 4 months, and 215 ± 12 and 180 ± 8 mmHg in the denervated one at 4 months, and 215 ± 12 and 180 ± 11, respectively, at 6 months.
Arterial wall/lumen ratios in the chronically denervated hemisphere were about 20% smaller at 4 months, and about 12% smaller at 6 months than those in the innervated hemisphere.
It was concluded that sympathetic dual effects, namely tonic and trophic actions, importantly contribute in the regulation of cerebral blood flow in response to acute elevation of arterial pressure in SHR.

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A population-based stroke death study was carried out in all prefectures of Japan between January 1963 and December 1983. The stroke death was significantly decreased approximately about 60% past 20 years in Japan. Seasonal variability of stroke death was demonstrated in many prefectures excluding Tokyo, Osaka, Hokkaido and Okinawa. The stroke death was highly significantly related to atmospheric temperature and consumption of fuel oil for heating in Japan past 20 yeras. Also there was a good correlation between the stroke death (cerebral hemorrhage) and heating-degree day which was corrected by consumption of fuel oil. These results suggested that cold temperature was significant risk factor for stroke death in Japan.

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Three case of brainstem vascular malformation were reported. Case 1, 32 year-old man, presented with left-sided ptosis and mild right hemiparesis, was clinically diagnosed to have Weber's syndrome. Vertebral angiography showed medullary veins with a medusa like pattern and computed tomography (CT) demonstrated a ring-like high density in the left cerebral peduncle and left thalamus. This case was considered to have a venous angioma of the midbrain and the thalamus neuroradiologically. Case 2, 58 year-old woman, and case 3, 53 year-old woman, were thought to have been multiple sclerosis (MS) at some time in their courses because of their progressive and intermittent clinical courses. Vertebral angiography of case 2 showed large draining veins in the dorsal aspect of the pons. CT scan demonstrated an enhansing round density area without a mass effect in the pons. The lesion was suggestive of a venous angioma. Vertebral angiography of case 3 showed no abnormal findings. However, CT scan showed an enhansing nodular density area in the right side of the pons and the medulla oblongata. The lesion was also suggestive to be a vascular malformation. The patients with the progressive and intermittent neurological signs and symptoms due to brainstem vascular malformation can be quite difficult to differentiate from other diseases such as MS, brainstem glioma or brainstem encephalitis. It is stressed that the patients with these kinds of clinical history should be carefully examined neurologically and neuroradiologically.

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Electrolyte and fluid disturbance was studied in a series of 54 patients with subarachnoid hemorrhage and 43 with intracerebral hematoma. All of the patients were hospitalized directly within 6 hours of onset. Nearly half of the cases presented hypokalemia (serum K<3.4 mEq/l) and hyperglycemia on admission, which returned to normal or near normal spontaneously within a few days. Severity of hypokalemia and hyperglycemia seemed correlated with neurological severity and subsequent mortality, but not with the site of hematoma. In the hypokalemic group, the level of serum catecholamin was significantly higher, but urinary potassium, serum insulin and blood gases remained within normal limits. A likely explanation is that this transient hypokalemia is due to a shift of potassium into the cells rather than a true body depletion, possibly caused by an overactivity of sympathetic nervous system.

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The effects of long-term cigarette smoking on regional cerebral blood flow (rCBF) were studied in 67 normal male volunteers.
They were divided into four groups of (1) 15 young smokers (mean age of 55 years), (2) 14 young non-smokers (mean age of 52 years), (3) 16 elderly smokers (mean age of 74 years), and (4) elderly non-smokers (mean age of 75 years). All subjects were healthy volunteers without any past history of cerebral and pulmonary diseases.
The rCBF was measured by Xe¹³³ inhalation method using 16-ch-Novo-cerebrograph. Pulmonary functions such as FVC, FEV_1.0%, %VC, FEV_1.0, V₅₀ and V₂₅ were measured by Autospiror HI-498, and End-tidal partial pressures for carbon dioxide (PeCO₂) were monitored by capnograph (Normocap, Datex).
The rCBF reduced significantly with advancing age. Although there was no significant difference in rCBF between young smokers and non-smokers, elderly smokers showed significantly lower rCBF than elderly nonsmokers. There was no difference in vital capacity and FEV_1.0% between smokers and non-smokers in both young and elderly people. Smokers group, however, showed significantly lower V₅₀ than non-smokers group. PeCO₂ in smokers was significantly lower than that in non-smokers. No significant differences were seen in hematocrit, antithrombin III, serum lipids, and blood pressure between two groups in the young and elderly. There was a signficantly positive correlation between rCBF and PeCO₂.
Our finding showed smoking over a long period produces reductions in the cerebral blood flow. This was consistent with the reports by other researchers. In addition, the results of the present study suggested the possibility that the latent small airway disturbances resulting from long-term smoking also play a role of leading to decreased PCO₂ and eventually cause reductions in rCBF.

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Findings of brain CT and cerebral angiogram in acute stage were analized in patients with embolic and thrombotic cerebral artery occlusion in relation with their mortality.
Thirty-three (17.8%) of 186 consecutive patients with embolic and 8 (5.6%) of 142 patients with thrombotic occlusion of the cerebral artery died during acute stage. Among them, 20 of embolic and 4 of thrombotic cases died due to tonsillar herniation within 10 days after onset. All of them presented with angiographic occlusions of more than two main cerebral arteries or the internal carotid artery with poor collateral circulation to regions normally supplied by the anterior and middle cerebral arteries.
Thiry-nine percent of the embolic group and 6% of the thrombotic group showed a shift of midline structures on CT. A ratio of the shift of the midline structures to the maximum width of the hemisphere on CT was computed to represent a degree of mass effect (midline shift index, MLS-I). The majority of patients who died of tonsillar herniation showed MLS-I greater than 10% on the Day 2 and/or that greater than 20% on the Day 3. Only four survived among the patients who met the above criteria.
The size of the infarct on CT (Infarct Indices) was significantly larger in embolic group than in thrombotic group. Infarct-Indices in patients who died due to herniation were greater than 66% and hypodense areas in these patients occupied more than entire region normally supplied by the middle cerebral artery.
Hemorrhagic transformation evaluated by CT was found in 41% of non fatal patients with embolic infarction, while in only 16% of those who died due to tonsillar herniation.

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475 patients with ischemic cerebrovascular disease were entered into a clinical trial to determine whether antiplatelet drugs would produce a significant reduction in the subsequent occurrence of cerebral infarction. The combination of antiplatelet drug and dipyridamole (DP), ifenprodil tartrate (IT) were also evaluated. Among the 475 patients of study population, 108 were in the aspirin (ASA) group, 199 in the ticlopidine group and 168 in the antiplatelet drug free group. Each regimen was consisted of ASA which dose was from 250 mg/day to 1500 mg/day or of TP which dose was from 200 mg/day to 300 mg/day. Those patients were followed up for 30 months. Reccurent cerebral infarction, site of lesion, drug doses, sex difference, blood pressure control, side effects of drugs were assesed.
At the end of study, the number of recurrent cerebral infarctions was 15 (13.9%) in the ASA group, 18 (9%) in the TP group and 40 (23.8%) in the antiplatelet drug free group. Life table analysis indicated significant differences between the treatment group (ASA group + TP group) and the antiplatelet drug free group (p<0.001). ASA group and TP group were essentially identical. Furthermore, significant differences were not found among ASA doses and among the combination of DP or IT. There was no significant sex differences in the efficacy of the antiplatelet drugs.
The antiplatelet drugs were effective in carotid cortical branch thrombosis and in carotid penetrating branch thrombosis, but there was no statistical difference in vertebrobasilar thrombosis. The trend was observed that the recurrent thrombosis occured in the same cortical branch territory and in the patient with poor blood pressure control. Cerebral hemorrhage was seen in 4 cases of all patients, of which 2 cases had 1500 mg of ASA, 1 case had TP and 1 case was the antiplatelet drug free group. It was supposed that high dose of ASA so suppressed platelet function that induced hemorrhagic events. However, there was no significant differences in the hemorrhagic events. Other side effects were not important.
It is concluded that the antiplatelet drugs have significantly benefitcial effect in the secondary prevention of atherothrombotic cerebral infarction.

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In five consecutive patients with a proven aneurysmal subarachnoid hemorrhage and undergoing neck clipping of aneurysm, the time course of vasospasm was monitored with transcranial Doppler sonography by serial measurements of the blood flow in bilacteral middle cerebral arteries. Sound-spectrogram specific to stenosis was detected from the middle cerebral arteries which was accompanied with increase of the time-mean velocity of the upper spectrum and decrease of the S/D ratio (maximum systolic to diastolic flow ratio). Stenotic flow pattern developed temporarily around 2 weeks after subarachnoid hemorrhage in one and 10 days after in the other. Transcranial Doppler sonography is considered to help us understand cerebral hemodynamics after subarachnoid hemorrhage including the time course and extent of vasospasm and the effect of the various antispastic treatments. This newly developed diagnostic tool will contribute information to the early diagnosis and early treatment of vasospasm.

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A case of persistent primitive trigeminal artery (PTA) associated with multiple cerebral aneurysms is reported.
A 54-year-old woman who had complained of diplopia had sudden headache, and she was admitted to our hospital on August 10, 1985. Neurological examination revealed that she had a right abducens nerve paralysis, resting tremor of left upper extremity and stiff neck. Computed tomography scan demonstrated subarachnoid hemorrhage. Right carotid angiography showed right PTA, intracavernous aneurysm of the internal carotid artery and aneurysm of the anterior communicating artery. On August 14, the neck of the aneurysm of the anterior communicating artery was clipped successfully.
To our knowledge, 48 cases of PTA associated with cerebral aneurysm have been reported in the literature. We have classified 28 cases (40 cerebral aneurysms) of the 48 cases, in which angiographic findings were described in detail, on the bais of Agnoli's classification. Of the 28 cases, 16 belong to type I, 15 to type II, 4 to type III, and 3 to type IV. The most common location of the associated 40 aneurysms is the PTA itself, an incidence of 11 aneurysms (25%). 9 aneurysms arise from the IC-PC junction. Then 16 aneurysms (40%) originate from the ipsilateral internal carotid artery, and 4 (10%) from the vertebro-basilar artery. With these findings, it is possible that the presence of a structural defect in the arterial walls, especially PTA itself, and the increased hemodynamic stress produced by PTA, acting on PTA itself, the ipsilateral internal carotid artery, and vertebro-basilar artery, play an important role in the development and rupture of the aneurysm.

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The effects of hematocrit (Ht) on the nemodynamics of antegrade and retrograde collateral circulation were studied in sixty one patients with thrombotic internal carotid artery occlusion. According to the angiographic findings of the collateralls, the subjects were devided into the two groups; one the antegrade group (Group A : N=34), in whom the collateral flow was circulating in an anterograde manner through the circle of Willis; and the other the retrograde group (Group R : N=27), in whom the collateral flow was circulating in a retrograde manner through the branches of external carotid artery and/or leptomeningial anastomosis. Regional cerebral blood flow (rCBF) was measured by the 133-Xe inhalation methods in all the cases more than three weeks after the ictus, and a relationship between rCBF and Ht were analyzed.
In Group A, there was no significant correlation between Ht and rCBF (r= -0.13). On the other hand, in Group R, a significant correlation existed between rCBF and Ht (r=-0.40, p<0.05).
The results of the present study suggest that Ht may give more extensive effects on the hemodynamics of retrograde collaterals than that of anterograde collaterals. In the retrograde collaterals, the blood flow has to go through the resistence vessels twice, while once in the anterograde collaterals. The flow velocity in the former is, therefore, likely to be slower than that in the latter. This difference in flow velocity (shear rate) may contribute to the greater Ht effects on the retrograde collteral circulation. Likewise, the retrograde collaterals are generally longer in distance compared to the antegrade collaterals. This difference in distance may be another factor, which gives a greater sensitivity against Ht changes to the retrograde collaterals.

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Hemophilia is a congenital coagulation defect which results in marked impairment of the second phase of blood coagulation. We investigated serial changes in the blood coagulation and fibrinolytic systems following an intracerebral hemorrhage occurred in a patient with hemophilia A.
A 51-year-old male with mild hemophilia A was admitted to our hospital approximately 13 hours after the onset of left putaminal hemorrhage. Because the patient's condition had been relatively stable for nearly 24 hours after the onset, it was elected to observe him conservatively with factor VIII replacement therapy.
Plasma levels of antithrombin III and fibrinopeptide A (FAP), and those of plasminogen and fibrinopeptide B/314-42, as sensitive markers for thrombin and plasmin activities respectively, were measured serially following stroke. No singificant changes in these parameters were observed before factor VIII replacement therapy on the 1st day. An adequate VIII : C level in plasma was obtained shortly after factor VIII infusion, nevertheless plasma FPA levels were hardly elevated unitl the 3rd day. Correspondingly, the amount of hematoma on cranial CT scan had become markedly large with symptomatic progression during the 2nd to 3rd day. On the 3rd day, plasma FPA level was greatly elevated with the corresponding changes in the other parameters.
These results suggest that the markedly delayed appearance of thrombin activity in plasma may represent a defective hemostatic response to injury, that is, defect of thrombin generation and may have been strongly associated with the growth of intracerebral hematoma. Thus, it is concluded that the combined replacement with factor VIII and activated prothrombin complex concentrate containing thrombin and activated factor X, which activate VIII : C protein, may be effective for an immediate and adequate appearance of hemostatic response.

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