Nitric oxide (NO) is considered to be associated with the pathogenesis of cerebral ischemic injury. The purpose of the present study was to investigate the effects of hyperglycemia on the NO production occurring during cerebral ischemia and reperfusion. Fourteen male Wister rats (250-330g) were anesthetized by in-traperitoneal injection of pentobarbital sodium. NO production was monitored continuously by in vivo microdialysis. Microdialysis probes were inserted into the left striaturn and hippocampus. The probes were perfused with Ringer' s solution at a constant rate of 2 ul/min. After a 2-hour equilibrium period, fractions were collected every 10 min. Laser Doppler probes were also inserted into the opposite side of the striatum and hippocamipus. In the normoglycemic group (n=7), forebrain cerebral ischemia was produced by ligation of the bilateral common carotid arteries and systemic hypotension (MABP<5 mm Hg) by hemorrhage. After 20 min, the loops around both common carotid arteries were released and the blood was re-infused. In the hyper-glycemic group (n=7), the plasma glucose was increased to 28.2 mmol/l with 50% glucose i.v. at a constant rate of 2 ml/hr and cerebral ischamia was produced by the same method as above. The levels of NO metabo-lites, nitrite (NO_2-) and nitrate (NO_3-), in the dialysate were determined using the Griess reaction. During cerebral ischemia, the rCBF in the striatun decreased to 45.2±5.8% (mean±SE) and 26.3±4.8% of the base-line level in the hyperglycemic group and control group, respectively. There was no significant difference in hippocampal rCBF between the two groups. During ischemia, the change in total NO (sum of NO₂ and NO₃) in the striatum of the hyperglycemic group (103.5±9.5% of the baseline level) was higher than that of the con-trol group (64.3±6.8%). At 10 min after reperfusion, the change in NO3 in the striatum of the hyperglycemic group (64.2±8.9% of the baseline level) was greater than that of the control group (38.2±3.0%). In the hip-pocampus, there were no significant differences between the two groups. These in vivo data suggested a hy-perglycemia effect especially on the NO production in the striatum during cerebral ischemia and reperfusion. Nitric oxide may thus be an inportant mediator in the exacerbation of post-ischemic brain injury in hyperglycemic rats.

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We have been developing a new stroke management system based on an acute stroke unit with referral to a rehabilitation unit at another hospital (inter-hospital referral model) in contrast to the conventional system utilizing a combined acute and rehabilitation stroke unit at a single hospital (intra-hospital referrral model). The stroke management system in three acute stroke hospitals in Kumamoto was evaluated to clarify the fea-tures of this new system.
In total, 806 patients (459 men, 347 women ; age, 71.0±12.2 years old) with acute ischemic stroke admitted between May 1999 and April 2000 were prospectively enrolled into the study. All clinical data were sys-tematically documented including the final diagnosis of the stroke subtype (atherothrombotic, cardioembolic, lacunar, others or TIA), NIHSS, admission time after onset, length of hospital stay, condition at discharge and modied Rankin Scale (mRS). The most frequent stroke subtype was cardioembolic (29.4%). The average NIHSS was 8.2 (median, 5). Two-fifths of the patients were admitted within 3 hours of stroke onset. The length of hospital stay was 17.3±17.4 (median, 14) days. About 60% of the patients could walk at discharge. Two-fifths of all patients were discharged to their home, and 76.6% of them were discharged within 14 days. Another two-fifths of the patients were transferred to rehabilitation hospitals, and 62.1% of them were dis-charged within 21 days. Patients with mRS≤2 and≥4 represented 49.9% and 39.0% of all patients, respec-tively. Acute hospitals aim to provide intensive stroke care within 14 days. On the other hand, rehabilitatoin hospitals commence their program from the early stage of stroke. A community-oriented hospital-team cooperates to provide the stroke service in Kumamoto.

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It was shown previously that endothelin (ET) receptor antagonist (RO 61-1790) reversed the postischemic hypoperfusion and significantly increased the cerebral perfusion after transient ischemia and focal ischemia [4-h middle cerebral artery occlusion (MCAO)], respectively. The aim of the present study was to determine whether additional or repeated treatment with RO 61-1790 would reduce tissue injury in spontaneously hypertensive rats subjected to 24-h MCAO. RO 61-1790 (affinity for ET_A receptor approximately 1000-fold higher than for ET_B receptor) was a gift from Hoffmann-LaRoche Ltd. (Basel, Switzerland). Animals were injected twice with 10 mg/kg RO 61-1790 (5 min before MCAO and 5 h later) or 3 times with 10 mg/kg RO 61-1790 (5 min before MCAO) and 5 mg/kg RO 61-1790 (5 h and 8 h later). Animals injected with vehicle (saline) at identical time intervals served as controls. Ischemic lesion volume was assessed on the basis of 2% 2, 3, 5-triphenyltetrazolium-chloride monohydrate (TTC) staining using an image analyzer (NIH Image). There were no significant differences in cerebral infarct volume between the animals injected twice with RO 61-1790 and the respective controls (165.2 ± 22.2 mm³ vs. 174.8 ± 20.5 mm³, respectively). However, the infarct volumes in the animals injected 3 times with RO 61-1790 (147.5±18.9 mm³) were significantly decreased as compared to the controls (178.4±12.1 mm³). These findings indicate that treatment with the ET_A antagonist, RO 61-1790, can ameliorate the cerebral infarct volume induced by MCAO. This effect is dependent upon the time and dose of RO 61-1790 treatment.

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The purpose of the present study was to clarify the etiological mechanisms of small pontine infarctions using diffusion-weighted magnetic resonance imaging (DWI). We investigated 26 consecutive patients with acute pontine infarctions of which the lesions were localized within the pons on DWI performed within 7 days after the onset. DWI revealed pontine infarctions extending to the basal surface in 15 patients (group 1) and deep pontine infarctions without extension to the basal surface in 10 patients (group 2). One patient whose DWI showed two pontine infarctions (one extended to the basal surface and the other did not) was excluded from subsequent analysis. Multiple extrapontine high intensity regions were observed in one patient of group 1 (hemodynamic infarction) and in 5 patients of group 2 (embolic infarctions), the difference being statistically significant (p=0.02). The patients' background, clinical course and MR angiography findings were compared between the two groups. Diabetes mellitus, fluctuations or progression of neurologic deficits during the acute stage and intracranial arterial stenosis were more frequently observed in group 1 than in group 2. These findings suggest that the etiological mechanism of pontine infarction in group 1 probably involved large-vessel disease or branch atheromatous disease, while that in group 2 appeared to be embolic (artery-to-artery or cardioembolic) or due to hypertensive small-vessel disease.

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Background : The clinical significance of cerebral microlesions of less than 3 mm in diameter observed on magnetic resonance imaging (MRI) remains unclear.
Patients : In total, 390 cases with localized lesions in the lacuna of less than 15 mm in diameter were studied.
Method : Microlesions with clear margins that were less than 3 mm in diameter were categorized as low, iso or high intensity separately on each T1-weighted image (T1WI), T2-weighted image (T2WI), protonweighted image or fluid attenuated inversion recovery (FLAIR) image. The correlation between microlesions and vascular risk factors was analyzed by logistic regression analysis and the influence of microlesions on brain infarction was investigated using Cox's proportional hazards model.
Results : Microlesions were frequently observed in the anterior perforated substance, basal ganglia, and subcortical white matter. Microlesions of the basal ganglia were correlated to age and hypertension, and those of the subcortical white matter were correlated to systolic blood pressure and fasting blood sugar. Microlesions of the basal ganglia or subcortical white matter displaying a low intensity on T1WI and a high intensity on T2WI were particulary associated with risk factors. Microlesions of the anterior perforated substance did not correlate strongly with any of the risk factors. Twenty-nine of the 390 cases suffered from brain infarction during the follow-up period. Patients with multiple microlesions of the upper basal ganglia showing a low intensity on T1WI, high intensity on T2WI, and low intensity on proton or FLAIR images, more frequently developed brain infarction.
Conclusion : The clinical significance of microlesions of the anterior perforated substance is low, but microlesions of the upper basal ganglia appear to be a predictive factor of brain infarction.

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[Purpose] We studied platelet activation in patients with MRI-proven cerebral infarction at the acute (ACI) and chronic (CCI) stages, as well as in age-matched controls by a flow cytometric method using monoclonal antibodies against activation-related molecules.
[Methods] Twenty-six patients with ACI, 59 patients with CCI and 26 age-matched control subjects were enrolled in the study. Platelet activation was measured by flow cytometry using monoclonal antibodies against CD62P and platelet fibrinogen receptor (PAC-1), two molecules which are expressed on the platelet surface in association with activation.
[Results and Conclusion] CD62P-and PAC-1-positive platelets were significantly increased in patients with ACI and CCI as compared to the controls. The percentage of CD62P-positive platelets was significantly higher in patients with ACI than in those with CCI. Among the patients with CCI, platelets positive for CD62P and for PAC-1 were significantly increased in those with atherothrombotic cerebral infarction as compared to those with lacunar infarction. These findings suggest that different mechanisms of platelet activation exist in these stroke subtypes.

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Background and Purpose Since an advent of MRI, the clinical diagnosis of medullary infarction has been made possible, and such cases seem to be increasing. Therefore, we reviewed recent cases of medullary infarction verified by MRI, and examined its epidemiological, clinical, and MR imaging features.
Subjects and Methods The survey was made on cases of medullary infarction diagnosed by brain MRI at 34 hospitals in Tohoku district, Japan, from 1996 to 2000. The analysis was mainly based on questionnaires, and, if MRI films were available, a neuroradiologist evaluated them.
Results Two hundreds fourteen cases of medullary infarction were collected, consisting of 167 (78%) cases of lateral medullary infarction (LMI), 41 (19%) of medial medullary infarction (MMI), and 6 (3%) of both medial and lateral medullary infarction. The mean age of onset and the man to woman ratio were 60.7 year old, 2.7:1 in LMI, and 65.0 year old, 3.6:1 in MMI, respectively. The middle medulla was most frequently affected in LMI, and the upper medulla in MMI. In both types, vascular changes including arterial dissection were observed in the vertebral arteries. Severe cases were much fewer than previously reported. There was no difference of the prognosis between LMI and MMI. Diabetes mellitus was more frequently associated with MMI than LMI or controls.
Conclusions The present study analyszed the world-largest number of cases of medullary infarction, and revealed many common and different aspects between LMI and MMI.

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Evidence-based medicine (EBM) has been emphasized in Japan for these years. In management of acute stroke, prospective stroke registries and randomized controlled trials have provided evidence that helps us examine and treat patients with acute stroke. Unfortunately evidence in stroke management has almost always been imported into Japan from the Western countries.
In order to obtain reliable large-scale data on stroke management, the Japan Multicenter Stroke Investigators' Collaboration (J-MUSIC) conducted a multicenter study. A total of 16, 922 patients with acute ischemic stroke admitted to 156 hospitals within 7 days after stroke onset were prospectively registered during the study period of one year. The study clearly demonstrated age, sex, onset to arrival time, neurological deficits, stroke subtypes, length of hospital stay, and clinical outcome of the patients and the current status of acute ischemic management. The study provided results supporting potential efficacy of hyperacute local thrombolytic therapy with urokinase.
In order to succeed to the fruits of the J-MUSIC study, the Japanese Standard Stroke Registration Study (JSSRS) was organized and completed a computer software for electronically collected database of acute stroke patients. The JSSRS database will be used for the nation-wide stroke registry, so-called Japan Acute Stroke Data Bank, and will help establish EBM for acute stroke in Japan.

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There is only a few evidence for stroke management has been reported from Japan. It is necessary to make a data bank of acute stroke patients as infrastructure to make evidence for standardization of stroke management. We made Japan standard stroke registry study (JSSRS) supported by ministry of health and welfare from 1999 to 2002. We completed computerized registry system and accumulated about 8, 000 acute stroke cases from 45 stroke center hospitals. This system is also functioning as a stroke database for each hospital. From the analysis of the distribution of stroke subtype, the incidence of atherothrombotic infarction and cardiogenic embolism was similar to lacunar infarction as shown in Figure 1. Furthermore, the 38% of ischemic stroke patients admitted within 3 hours. Thrombolytic therapy was performed in 15% of the patients who admitted within 3 hours and their initial severity were NIHSS 6-29. The outcome of the patients treated with thrombolytic therapy was significantly better than those without it. These data indicate that the stroke data bank should be useful tool to make verification of the guideline and planning a clinical trial for EBM in near future.

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