| NO mediates microglial response to acute spinal cord injury under ATP control in vivo. | |
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MedLine Citation:
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PMID: 20468054 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To understand the pathomechanisms of spinal cord injuries will be a prerequisite to develop efficient therapies. By investigating acute lesions of spinal cord white matter in anesthetized mice with fluorescently labeled microglia and axons using in vivo two-photon laser-scanning microscopy (2P-LSM), we identified the messenger nitric oxide (NO) as a modulator of injury-activated microglia. Local tissue damages evoked by high-power laser pulses provoked an immediate attraction of microglial processes. Spinal superfusion with NO synthase and guanylate cyclase inhibitors blocked these extensions. Furthermore, local injection of the NO-donor spermine NONOate (SPNO) or the NO-dependent second messenger cGMP induced efficient migration of microglial cells toward the injection site. High-tissue levels of NO, achieved by uniform superfusion with SPNO and mimicking extended tissue damage, resulted in a fast conversion of the microglial shape from ramified to ameboid indicating cellular activation. When the spinal white matter was preconditioned by increased, ambient ATP (known as a microglial chemoattractant) levels, the attraction of microglial processes to local NO release was augmented, whereas it was abolished at low levels of tissue ATP. Because both signaling molecules, NO and ATP, mediate acute microglial reactions, coordinated pharmacological targeting of NO and purinergic pathways will be an effective mean to influence the innate immune processes after spinal cord injury. |
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Authors:
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Payam Dibaj; Fabien Nadrigny; Heinz Steffens; Anja Scheller; Johannes Hirrlinger; Eike D Schomburg; Clemens Neusch; Frank Kirchhoff |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Glia Volume: 58 ISSN: 1098-1136 ISO Abbreviation: Glia Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-05-14 Completed Date: 2010-08-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8806785 Medline TA: Glia Country: United States |
Other Details:
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Languages: eng Pagination: 1133-44 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Wiley-Liss, Inc. |
Affiliation:
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Department of Neurology, Georg August University of Göttingen, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acute Disease Adenosine Triphosphate / metabolism* Animals Axons / drug effects, physiology Cell Movement / drug effects, physiology Cell Polarity / drug effects, physiology Cyclic GMP / metabolism Enzyme Inhibitors / pharmacology Guanylate Cyclase / antagonists & inhibitors, metabolism Mice Mice, Transgenic Microglia / cytology, drug effects, physiology* Nerve Fibers, Myelinated / drug effects, physiology Nitric Oxide / metabolism* Nitric Oxide Donors / pharmacology Nitric Oxide Synthase / antagonists & inhibitors, metabolism Signal Transduction / drug effects Spermine / analogs & derivatives, pharmacology Spinal Cord / drug effects, physiopathology Spinal Cord Injuries / physiopathology* |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Nitric Oxide Donors; 10102-43-9/Nitric Oxide; 136587-13-8/spermine nitric oxide complex; 56-65-5/Adenosine Triphosphate; 71-44-3/Spermine; 7665-99-8/Cyclic GMP; EC 1.14.13.39/Nitric Oxide Synthase; EC 4.6.1.2/Guanylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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