Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain

التفاصيل البيبلوغرافية
العنوان: Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain
المؤلفون: Howe, Charles L, LaFrance-Corey, Reghann G, Sundsbak, Rhianna S, LaFrance, Stephanie J
بيانات النشر: BioMed Central Ltd.
سنة النشر: 2012
المجموعة: BioMed Central
مصطلحات موضوعية: 1A8, alveus, brain-infiltrating leukocytes, CD11b, Gr1, hippocampus, inflammatory monocyte, macrophage, neutrophil, LysM:GFP reporter mouse, Ly6C, Ly6G, Theiler's virus
الوصف: Background Neuropathology caused by acute viral infection of the brain is associated with the development of persistent neurological deficits. Identification of the immune effectors responsible for injuring the brain during acute infection is necessary for the development of therapeutic strategies that reduce neuropathology but maintain immune control of the virus. Methods The identity of brain-infiltrating leukocytes was determined using microscopy and flow cytometry at several acute time points following intracranial infection of mice with the Theiler's murine encephalomyelitis virus. Behavioral consequences of immune cell depletion were assessed by Morris water maze. Results Inflammatory monocytes, defined as CD45 hi CD11b ++ F4/80 + Gr1 + 1A8 - , and neutrophils, defined as CD45 hi CD11b +++ F4/80 - Gr1 + 1A8 + , were found in the brain at 12 h after infection. Flow cytometry of brain-infiltrating leukocytes collected from LysM: GFP reporter mice confirmed the identification of neutrophils and inflammatory monocytes in the brain. Microscopy of sections from infected LysM:GFP mice showed that infiltrating cells were concentrated in the hippocampal formation. Immunostaining confirmed that neutrophils and inflammatory monocytes were localized to the hippocampal formation at 12 h after infection. Immunodepletion of inflammatory monocytes and neutrophils but not of neutrophils only resulted in preservation of hippocampal neurons. Immunodepletion of inflammatory monocytes also preserved cognitive function as assessed by the Morris water maze. Conclusions Neutrophils and inflammatory monocytes rapidly and robustly responded to Theiler's virus infection by infiltrating the brain. Inflammatory monocytes preceded neutrophils, but both cell types were present in the hippocampal formation at a timepoint that is consistent with a role in triggering hippocampal pathology. Depletion of inflammatory monocytes and neutrophils with the Gr1 antibody resulted in hippocampal neuroprotection and preservation of cognitive ...
نوع الوثيقة: report
اللغة: English
العلاقة: http://www.jneuroinflammation.com/content/9/1/50Test
الإتاحة: http://www.jneuroinflammation.com/content/9/1/50Test
حقوق: Copyright 2012 Howe et al; licensee BioMed Central Ltd.
رقم الانضمام: edsbas.273DA0B7
قاعدة البيانات: BASE