Cerebral ischemia/reperfusion (I/R) injury is a critical factor leading to a poor prognosis for ischemic stroke patients. ω-3 fatty acid supplements taken as part of a daily diet have been shown to improve the prognosis of patients with ischemic stroke. In this study, we aimed to investigate the potential effects of resolvin D2 (RvD2), a derivative of ω-3 fatty acids, and its possible advantage on cerebral I/R injury in rats. Cerebral I/R caused by middle cerebral artery occlusion and reperfusion (MCAO/R) was established in Sprague-Dawley rats. First, in rats fed a regular diet, the MCAO/R stimulus led to a significant decrease in endogenous production of RvD2. Exogenous supply of RvD2 via intraperitoneal injection reversed MCAO/R-induced brain injury, including infarction, inflammatory response, brain edema, and neurological dysfunction. Meanwhile, RvD2 reversed the MCAO/R-induced decrease in the protein level of GPR18, which has been identified as a receptor for RvD2, especially in neurons and brain microvascular endothelial cells (BMVECs). Furthermore, RvD2 exerted rescue effects on MCAO/R-induced neuron and BMVEC death. Moreover, GPR18 antagonist O-1918 could block the rescue effects of RvD2, possibly at least partially though the GPR18-ERK1/2-NOS signaling pathway. Finally, compared with ω-3 fatty acid supplements, RvD2 treatment had a better rescue effect on cerebral infarction, which may be due to the MCAO/R-induced decrease in 5-lipoxygense phosphorylation and subsequent RvD2 generation. In conclusion, compared with ω-3 fatty acids, RvD2 may be an optimal alternative and complementary treatment for ischemic stroke patients with recanalization treatment.
SummaryAtrial fibrillation (AF) is the most common clinically relevant arrhythmia. AF is a strong independent risk factor for the subsequent development of heart failure (HF). HF and AF can interact to perpetuate and exacerbate each other. Soluble ST2 (sST2) is a biomarker of cardiomyocyte stretch that is useful in the diagnosis and prognosis of HF. Its role in the field of AF has not yet been well investigated. We studied the concentration of sST2 in a cohort of 174 subjects (62.1% men; mean age, 65.6 ± 10.3 years [± standard deviation (SD)]) with nonvalvular AF and 116 age-matched patients with sinus rhythm (SR). Subjects were subdivided into 3 groups: paroxysmal AF, persistent AF, and SR. Plasma sST2 concentrations were measured using an electrochemiluminescence-based immunoassay. The sST2 level was higher in persistent AF patients (P < 0.05) and paroxysmal AF patients (P < 0.05) than in SR patients. No significant difference was found between persistent AF and paroxysmal AF. sST2 was correlated with left atrial diameter (LAD) (r = 0.21; P < 0.01). During a median follow-up time of 6 months, 43 subjects with non-valvular AF in the study had HF. Cox proportional hazard analysis revealed both sST2 and LAD were independent predictors of HF. sST2 concentrations are higher in AF than SR. Plasma sST2 may be a useful biomarker in predicting HF in patients with AF.(Int Heart J 2018; 59: 58-63)
BackgroundEosinophilic myocarditis (EM) is a relatively rare condition that may result from parasitic infections and allergic disease. Antituberculosis drugs may lead to focal myocardial infiltration by eosinophils (eosinophilic myocarditis). Symptoms may be severe, and, lead to rapidly-fatal outcomes. Early diagnosis and high-dose corticosteroids are the cornerstone of treatment, and, may lead to restoration of cardiac function with full recovery.Case presentationWe report a case of eosinophilic myocarditis secondary to eosinophilia caused by antituberculosis drugs with markedly elevated ECP, focal eosinophilic infiltration in CMR imaging and endomyocardial biopsy. Finally, high-dose corticosteroids were used to reverse the cardiac injury and to improve the clinical outcome.ConclusionAntituberculosis drugs can cause eosinophilic infiltration of, and damage to, the myocardium leading to rapid progression of the clinical symptoms. Myocardial biopsy is helpful in diagnosing the disease in the early stages and high-dose corticosteroids effectively improves the prognosis of this disease.
The infiltration of blood components into the brain parenchyma through the lymphoid system is an important cause of subarachnoid hemorrhage injury. AQP4, a water channel protein located at the astrocyte foot, has been reported to regulate blood–brain barrier integrity, and its polarization is disrupted after SAH. Neuronal ferroptosis is involved in subarachnoid hemorrhage- (SAH-) induced brain injury, but the inducing factors are not completely clear. Transferrin is one of the inducing factors of ferroptosis. This study is aimed at researching the role and mechanism of AQP4 in brain injury after subarachnoid hemorrhage in mice. An experimental mouse SAH model was established by endovascular perforation. An AAV vector encoding AQP4 with a GFAP-specific promoter was administered to mice to achieve specific overexpression of AQP4 in astrocytes. PI staining, Fer-1 intervention, and transmission electron microscopy were used to detect neuronal ferroptosis, and dextran (40 kD) leakage was used to detect BBB integrity. Western blot analysis of perfused brain tissue protein samples was used to detect transferrin infiltration. First, neuronal ferroptosis 24 h after SAH was observed by PI staining and Fer-1 intervention. Second, a significant increase in transferrin infiltration was found in the brain parenchyma 24 h after SAH modeling, while transferrin content was positively correlated with neuronal ferroptosis. Then, we observed that AQP4 overexpression effectively improved AQP depolarization and BBB injury induced by SAH and significantly reduced transferrin infiltration and neuronal ferroptosis after SAH. Finally, we found that AQP4 overexpression could effectively improve the neurobehavioral ability of SAH mice, and the neurobehavioral ability was negatively correlated with transferrin brain content. Taken together, these data indicate that overexpression of AQP4 in the mouse brain can effectively improve post-SAH neuronal ferroptosis and brain injury, at least partly by inhibiting transferrin infiltration into the brain parenchyma in the glymphatic system.
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