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BackgroundVascular endothelial growth factor (VEGF) is a well-known molecule mediating neuronal survival and angiogenesis. However, its clinical significance in ischemic stroke is still controversial. The goal of this study was to examine the temporal profile of plasma VEGF value and its clinical significance in ischemic stroke with taking its subtypes into consideration.MethodsWe prospectively enrolled 171 patients with ischemic stroke and age- and gender-matched healthy subjects. The stroke patients were divided into 4 subtypes: atherothrombotic infarction (ATBI, n = 34), lacunar infarction (LAC, n = 45), cardioembolic infarction (CE, n = 49) and other types (OT, n = 43). Plasma VEGF values were measured as a part of multiplex immunoassay (Human MAP v1.6) and we obtained clinical information at 5 time points (days 0, 3, 7, 14 and 90) after the stroke onset.ResultsPlasma VEGF values were significantly higher in all stroke subtypes but OT than those in the controls throughout 90 days after stroke onset. There was no significant difference in the average VEGF values among ATBI, LAC, and CE. VEGF values were positively associated with neurological severity in CE patients, while a negative association was found in ATBI patients. After adjustment for possible confounding factors, plasma VEGF value was an independent predictor of poor functional outcome in CE patients.ConclusionsAlthough plasma VEGF value increases immediately after the stroke onset equally in all stroke subtypes, its significance in functional outcome may be different among the stroke subtypes.

Background and Purpose-Recent studies show that successful endovascular thrombectomy 6 to 12 hours after stroke onset enhances functional outcomes 3 months later. In this study, we investigated the effects of reperfusion after ischemia on repair processes in the ischemic areas, as well as on functional recovery, using mouse stroke models. Methods-We examined time-dependent histological changes and functional recovery after transient middle cerebral artery occlusion of different durations, including permanent middle cerebral artery occlusion, using the CB-17 (CB-17/lcr-+/+Jcl) mouse strain, which has poor pial collateral blood flow. Results-Large microtubule-associated protein 2-negative areas of neuronal death were produced in mice subjected to ≥60 minutes of ischemia followed by reperfusion on day 1, while restricted microtubule-associated protein 2-negative regions were observed in mice subjected to a 45-minute period of ischemia. A substantial reduction in microtubule-associated protein 2-negative areas was observed on day 7 in mice given early reperfusion and was associated with better functional recovery. Klüver-Barrera staining demonstrated that white matter injury on day 1 was significantly lesser in mice with reperfusion. Immunohistochemistry and electron microscopy revealed that a greater number of endothelial cells were present in the infarct areas in mice with earlier reperfusion and were associated with a more rapid recruitment of plateletderived growth factor receptor β-positive pericytes and subsequent intrainfarct fibrosis. Early reperfusion also resulted in a greater accumulation of glial fibrillary acidic protein-positive astrocytes in peri-infarct areas. Peri-infarct astrogliosis was attenuated in platelet-derived growth factor receptor β heterozygous knockout mice. Conclusions-Early reperfusion after ischemia enhances the survival of endothelial cells and pericytes within ischemic areas even after the infarct is established, resulting in efficient intrainfarct fibrosis and peri-infarct astrogliosis. These effects might be associated with efficient peri-infarct reorganization and functional recovery. in peri-infarct areas in experimental researches, although this remains controversial. 21,22 Furthermore, it is experimentally suggested that efficient fibrotic formation within areas of infarct may promote peri-infarct astrogliosis. 23 Thus, if these repair processes are associated with functional recovery, apparent infarct volumes at early phases may not be suitable for predicting functional outcome.To date, few papers have focused on the effects of reperfusion on poststroke repair processes in both animals and human. In the present study, we hypothesized that early reperfusion might elicit efficient tissue repair, such as intrainfarct fibrosis and peri-infarct astrogliosis, and lead to functional recovery even if it does not prevent neuronal death within the ischemic areas. To examine the precise effects of ischemia-reperfusion in the MCA, we performed tMCAO of various durations, as well as perm...

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Background: The effects of lipid levels on clinical outcomes after ischemic stroke are controversial. Whether admission lipid levels and prior statin use are associated with early intracerebral hemorrhage (ICH) and long-term functional outcome after recombinant tissue plasminogen activator (rt-PA) therapy for stroke patients was investigated. Methods: Ischemic stroke patients who received intravenous rt-PA from a multicenter registry were studied. Lipid levels on admission, including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglyceride levels, as well as prior statin use, were assessed. The primary outcome was favorable outcome at 3 months corresponding to a modified Rankin Scale score ≤1. The secondary outcome was any or symptomatic ICH within the initial 36 h. Results: Of 489 enrolled patients (171 women, 70.8 ± 11.6 years old), 60 used statins prior to stroke, 93 developed ICH (19.0%), and 188 (38.4%) had a favorable 3-month outcome. Of the lipid levels, only the HDL-C level was an independent predictor of favorable outcome after multivariate adjustment for baseline characteristics (OR 1.95, 95% CI 1.10–3.47 per 1 mmol/l; p = 0.023) and after further adjustment for pretreatment radiological findings (OR 2.03, 95% CI 1.07–3.84; p = 0.029). For the 187 stroke patients without cardioembolism, the HDL-C level was more strongly associated with favorable outcome (OR 4.94, 95% CI 1.91–12.76 per 1 mmol/l; p = 0.001). There were no significant associations between ICH and any lipid levels. Prior statin use was not associated with outcomes. Conclusions: The admission HDL-C level was associated with favorable outcome 3 months after intravenous rt-PA therapy in stroke patients without cardioembolism.

Background: To determine the underlying conditions that affect the degree of calcification of carotid arterial plaques, measured quantitatively using multidetector row computed tomography (MDCT), and to study the association of carotid calcification with clinical symptomatology. Methods: We measured the calcification volume of stenotic lesions at the carotid bifurcation using MDCT in 84 consecutive patients who were scheduled to undergo carotid revascularization. These results were compared with the clinical and radiological characteristics of the patients. Results: On MDCT, calcification in the carotid plaques was present in 78 patients (93%). Compared to the other patients, patients in the highest quartile of calcification volume (quartile 4) had higher serum creatinine levels (p < 0.001) and tended to have fewer symptomatic ischemic events in the territory of the affected carotid artery in the preceding 6 months (29 vs. 49%, p = 0.099); in particular, there were fewer transient symptoms (5 vs. 27%, p = 0.032) and symptoms possibly occurring due to local embolism (14 vs. 37%, p = 0.045). On ultrasound, plaque ulceration was less prevalent in patients in quartile 4 than in the remaining patients (5 vs. 29%, p = 0.026), although the severity of carotid stenosis was similar among all the quartiles. Conclusions: Renal dysfunction was associated with enhanced carotid plaque calcification. Patients with severe carotid calcification were found to have a low risk of recent ischemic stroke, presumably due, in part, to a lower prevalence of emboligenic carotid ulceration. MDCT was valuable for the quantitative evaluation of carotid calcification.

Background: With the recent increase in the use of antithrombotic therapy, intracerebral hemorrhage (ICH) has been found to be a common complication. We determined whether the use of oral antithrombotic therapy and the patients’ preexisting comorbidities were predictive of cerebellar hemorrhage (CH; previously reported to be associated with anticoagulants) as compared to other ICH, and whether antithrombotic therapy affected the clinical severity of CH. Methods: A study of 327 consecutive patients hospitalized in our institute within 3 days after the onset of ICH, including 38 patients with a CH. Results: CH accounted for 12% of all ICH, 75% of which occurred in patients on warfarin therapy with an international normalized ratio (INR) for prothrombin time >2.5 (p < 0.0001), and 33% of which occurred in patients on ticlopidine therapy (p = 0.017). Warfarin therapy with an INR >2.5 and high blood glucose on admission were independently predictive of CH as compared to other ICH. In addition, previous ischemic stroke (p = 0.002) and heart diseases (p = 0.018) were more prevalent in patients with CH than in those with other ICH. The number of major arteriosclerotic comorbidities and risk factors was also independently predictive of CH risk. Conclusions: We confirmed that warfarin therapy with an INR >2.5 is associated with CH. Patients with CH frequently had arteriosclerotic comorbidities requiring antithrombotic therapy that can complicate their acute management.