Translational stroke research
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The role of phosphatidylserine (PS)-mediated procoagulant activity (PCA) in stroke remains unclear. To ascertain this role, early dynamic evolution of PS exposure on blood cells and released microparticles (MPs) and the corresponding PCA were evaluated in patients with acute ischemic stroke (AIS). Flow cytometry analyses revealed that initial levels of PS exposure on erythrocyte, platelet, and leukocyte were 2.40-, 1.36-, and 1.38-fold higher, respectively, in AIS than the risk factor-matched (RF) controls. ⋯ Thrombin generation promoted by platelets and MPs at 12 h was significantly higher in patients with cardioembolism than in patients without. The thrombophilic susceptibility of AIS patients can be partly ascribed to PS exposure on blood cells and the release of MPs. Our studies identify PS exposure as a potentially novel therapeutic target in the treatment of AIS.
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Oxidative stress plays an important role in cerebral ischemia-reperfusion injury. Dimethyl fumarate (DMF) and its primary metabolite monomethyl fumarate (MMF) are antioxidant agents that can activate the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and induce the expression of antioxidant proteins. Here, we evaluated the impact of DMF and MMF on ischemia-induced brain injury and whether the Nrf2 pathway mediates the effects provided by DMF and MMF in cerebral ischemia-reperfusion injury. ⋯ Further, DMF and MMF suppress glial activation following brain ischemia. Importantly, the protection of DMF and MMF was mostly evident during the subacute stage and was abolished in Nrf2-/- mice, indicating that the Nrf2 pathway is required for the beneficial effects of DMF and MMF. Together, our data indicate that DMF and MMF have therapeutic potential in cerebral ischemia-reperfusion injury and their protective role is likely mediated by the Nrf2 pathway.
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Anesthetics have enabled major advances in development of experimental models of human stroke. Yet, their profound pharmacologic effects on neural function can confound the interpretation of experimental stroke research. Anesthetics have species-, drug-, and dose-specific effects on cerebral blood flow and metabolism, neurovascular coupling, autoregulation, ischemic depolarizations, excitotoxicity, inflammation, neural networks, and numerous molecular pathways relevant for stroke outcome. ⋯ Anesthetics also modulate systemic arterial blood pressure, lung ventilation, and thermoregulation, all of which may interact with the ischemic insult as well as the therapeutic interventions. These confounds present a dilemma. Here, we provide an overview of the anesthetic mechanisms of action and molecular and physiologic effects on factors relevant to stroke outcomes that can guide the choice and optimization of the anesthetic regimen in experimental stroke.
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The present study investigates the association between hour-to-hour blood pressure (BP) variability and severe hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) during hyperacute stage. We analyzed hour-to-hour BP measurement within 24 h after IVT in patients with acute ischemic stroke. We calculated the maximum, minimum, and average (mean) of 24-h BP values, and BP variability profiles including standard deviation (SD), average squared difference between successive measurements (SV), average squared difference between rise and drop successive measurements (SV rise and SV drop), and maximum of SV rise and SV drop (SVrisemax and SVdropmax) after quartering 0-to-24 h BP course. ⋯ Binary logistic regression indicated that SBPSD and SBPSV within the first 24 h were associated with sICH (OR, 4.538; 95 % CI, 1.834-11.230; p = 0.001 and OR, 6.117; 95 % CI, 2.000-18.711; p = 0.002) and PH (OR, 2.146; 95 % CI, 1.106-4.165; p = 0.024 and OR, 2.202; 95 % CI, 1.046-4.633; p = 0.038). For the SBP SV parameters among four periods of the initial 24 h, only SV, SVrise, and SVrisemax during the first 6 h were significantly associated with sICH (OR, 2.785; 95 % CI, 1.294-5.994; p = 0.009; OR, 1.825; 95 % CI, 1.110-3.002; p = 0.018 and OR, 1.495; 95 % CI, 1.039-2.149; p = 0.030) and PH (OR, 2.088; 95 % CI, 1.287-3.387; p = 0.003; OR, 1.501; 95 % CI, 1.044-2.156; p = 0.028 and OR, 1.334; 95 % CI, 1.023-1.739; p = 0.033). High systolic BP variability during the first 6 h after IVT was related with severe HTs, which highlights the potential predictability to severe HTs.
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Evidence of the appropriate amount of fluid intake during the first few days after acute stroke was scarce. Concerns were raised in patients with acute malignant middle cerebral infarction, who tended to have malignant brain edema later. The purpose of the study was to evaluate the effect of fluid intake on the occurrence of malignant brain edema in patients with acute middle cerebral artery infarction. ⋯ Seventy-nine patients (79/184, 43%) died. In the subgroup of patients with malignant brain edema, 39 patients (39/65, 60%) died and only 11% (7/65 patients) had favorable outcome. High amount of fluid intake in the first few days of acute middle cerebral infarction was related to the occurrence of malignant brain edema.