| PEGylated interferon-beta modulates the acute inflammatory response and recovery when combined with forced exercise following cervical spinal contusion injury. | |
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MedLine Citation:
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PMID: 20109445 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Secondary degeneration leads to an expansion of the initial tissue damage sustained during a spinal cord injury (SCI). Dampening the cellular inflammatory response that contributes to this progressive tissue damage is one possible strategy for neuroprotection after acute SCI. We initially examined whether treatment with a PEGylated form of rat interferon-beta (IFN-beta) would modulate the expression of several markers of inflammation and neuroprotection at the site of a unilateral cervical level 5 contusion injury. Adult female Sprague-Dawley rats were injured using the Infinite Horizon Impactor at a force of 200 kdyn (equivalent to a severe injury) and a mean displacement of 1600-1800 mum. A single dose (5x10(6) units) of PEGylated IFN-beta or vehicle was administered 30 min following SCI. Here we demonstrate temporal changes in pro- and anti-inflammatory cytokine levels and the expression of heat shock proteins and iNOS (involved in neuroprotection) at the lesion epicenter and one segment caudally after SCI and PEG IFN-beta treatment. The results suggested a potential therapeutic treatment strategy for modulation of secondary damage after acute SCI. Therefore, we examined whether acute treatment with PEG IFN-beta would improve forelimb function alone or when combined with forced exercise (Ex). Animals began the Ex paradigm 5 days post SCI and continued for 5 days/week over 8 weeks. Locomotion (forelimb locomotor scale [FLS], hindlimb BBB, and TreadScan) and sensorimotor function (grid walking) was tested weekly. Additional outcome measures included lesion size and glial cell reactivity. Significant FLS improvements occurred at 1 week post SCI in the PEGylated IFN-beta-treated group but not at any other time point or with any other treatment approaches. These results suggest that this acute neuroprotective treatment strategy does not translate into long term behavioral recovery even when combined with forced exercise. |
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Authors:
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Harra R Sandrow-Feinberg; Victoria Zhukareva; Lauren Santi; Kassi Miller; Jed S Shumsky; Darren P Baker; John D Houle |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-01-28 |
Journal Detail:
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Title: Experimental neurology Volume: 223 ISSN: 1090-2430 ISO Abbreviation: Exp. Neurol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-04 Completed Date: 2010-07-01 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 0370712 Medline TA: Exp Neurol Country: United States |
Other Details:
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Languages: eng Pagination: 439-51 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2009 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acute Disease Animals Cervical Vertebrae Combined Modality Therapy Exercise Therapy* Female Forelimb / innervation, physiology Interferon-beta / immunology, pharmacology* Keratins / blood Locomotion / drug effects Myelitis / drug therapy*, immunology, pathology Neuroprotective Agents / immunology, pharmacology Polyethylene Glycols / pharmacology* Rats Rats, Sprague-Dawley Recovery of Function / drug effects* Spinal Cord Injuries / drug therapy*, immunology, pathology |
| Grant Support | |
ID/Acronym/Agency:
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NS26380/NS/NINDS NIH HHS; R37 NS026380-21/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Neuroprotective Agents; 0/Polyethylene Glycols; 68238-35-7/Keratins; 77238-31-4/Interferon-beta |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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