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Role of Neutrophilsin Exacerbation ofBrain Injury AfterFocal CerebralIschemia inHyperlipidemic Mice Josephine HerzPascal SabellekThomas E. Lane2015 год

Role of Neutrophils in Exacerbation of Brain Injury After Focal Cerebral Ischemia in Hyperlipidemic Mice
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Аннотация: Background and Purpose— Inflammation-related comorbidities contribute to stroke-induced immune responses and brain damage. We previously showed that hyperlipidemia exacerbates ischemic brain injury, which is associated with elevated peripheral and cerebral granulocyte numbers. Herein, we evaluate the contribution of neutrophils to the exacerbation of ischemic brain injury. Methods— Wild-type mice fed with a normal chow and ApoE knockout mice fed with a high cholesterol diet were exposed to middle cerebral artery occlusion. CXCR2 was blocked using the selective antagonist SB225002 (2 mg/kg) or neutralizing CXCR2 antiserum. Neutrophils were depleted using an anti-Ly6G antibody. At 72 hours post ischemia, immunohistochemistry, flow cytometry, and real-time polymerase chain reaction were performed to determine cerebral tissue injury and immunologic changes in the blood, bone marrow, and brain. Functional outcome was assessed by accelerated rota rod and tight rope tests at 4, 7, and 14 days post ischemia. Results— CXCR2 antagonization reduced neurological deficits and infarct volumes that were exacerbated in hyperlipidemic ApoE −/− mice. This effect was mimicked by neutrophil depletion. Cerebral neutrophil infiltration and peripheral neutrophilia, which were increased on ischemia in hyperlipidemia, were attenuated by CXCR2 antagonization. This downscaling of neutrophil responses was associated with increased neutrophil apoptosis and reduced levels of CXCR2, inducible nitric oxide synthase, and NADPH oxidase 2 expression on bone marrow neutrophils. Conclusions— Our data demonstrate a role of neutrophils in the exacerbation of ischemic brain injury induced by hyperlipidemia. Accordingly, CXCR2 blockade, which prevents neutrophil recruitment into the brain, might be an effective option for stroke treatment in patients with hyperlipidemia.
Год издания: 2015
Авторы: Josephine Herz, Pascal Sabellek, Thomas E. Lane, Matthias Gunzer, Dirk M. Hermann, Thorsten R. Doeppner
Издательство: Lippincott Williams & Wilkins
Источник: Stroke
Ключевые слова: Neurological Disorders and Treatments, S100 Proteins and Annexins, Neurological Disease Mechanisms and Treatments
Другие ссылки: Stroke (PDF)
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Europe PMC (PubMed Central) (PDF)
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eScholarship (California Digital Library) (PDF)
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