Document Detail


A novel role of phospholipase A2 in mediating spinal cord secondary injury.
MedLine Citation:
PMID:  16498630     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To investigate whether phospholipase A2 (PLA2) plays a role in the pathogenesis of spinal cord injury (SCI). METHODS: Biochemical, Western blot, histological, immunohistochemical, electron microscopic, electrophysiological, and behavior assessments were performed to investigate (1) SCI-induced PLA2 activity, expression, and cellular localization after a contusive SCI; and (2) the effects of exogenous PLA2 on spinal cord neuronal death in vitro and tissue damage, inflammation, and function in vivo. RESULTS: After SCI, both PLA2 activity and cytosolic PLA2 expression increased significantly, with cytosolic PLA2 expression being localized mainly in neurons and oligodendrocytes. Both PLA2 and melittin, an activator of endogenous PLA2, induced spinal neuronal death in vitro, which was substantially reversed by mepacrine, a PLA2 inhibitor. When PLA2 or melittin was microinjected into the normal spinal cord, the former induced confined demyelination and latter diffuse tissue necrosis. Both injections induced inflammation, oxidation, and tissue damage, resulting in corresponding electrophysiological and behavioral impairments. Importantly, the PLA2-induced demyelination was significantly reversed by mepacrine. INTERPRETATION: PLA2, increased significantly after SCI, may play a key role in mediating neuronal death and oligodendrocyte demyelination following SCI. Blocking PLA2 action may represent a novel repair strategy to reduce tissue damage and increase function after SCI.
Authors:
Nai-Kui Liu; Yi Ping Zhang; William Lee Titsworth; Xiaoyan Jiang; Shu Han; Pei-Hua Lu; Christopher B Shields; Xiao-Ming Xu
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of neurology     Volume:  59     ISSN:  0364-5134     ISO Abbreviation:  Ann. Neurol.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-04-03     Completed Date:  2006-06-02     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  606-19     Citation Subset:  IM    
Affiliation:
Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, KY 40292, USA.
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MeSH Terms
Descriptor/Qualifier:
Aldehydes / metabolism
Animals
Antigens, CD11b / metabolism
Apoptosis / drug effects
Blotting, Western / methods
Cell Count / methods
Cells, Cultured
Cytokines / metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Interactions
Embryo, Mammalian
Female
Gene Expression / drug effects
Glial Fibrillary Acidic Protein / metabolism
Hydro-Lyases / metabolism
Immunohistochemistry / methods
Intracellular Signaling Peptides and Proteins / metabolism
Melitten / administration & dosage
Microscopy, Electron, Transmission / methods
Motor Activity / drug effects,  physiology
Neurons / drug effects,  metabolism,  ultrastructure
Oligodendroglia / drug effects,  metabolism,  ultrastructure
Phospholipases A / administration & dosage,  physiology*
Phospholipases A2
Phosphopyruvate Hydratase / metabolism
Rats
Rats, Sprague-Dawley
Spinal Cord / cytology,  ultrastructure
Spinal Cord Injuries / complications,  drug therapy,  enzymology*
Time Factors
Grant Support
ID/Acronym/Agency:
NS36350/NS/NINDS NIH HHS; NS52290/NS/NINDS NIH HHS; RR15576/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Aldehydes; 0/Antigens, CD11b; 0/Cytokines; 0/Glial Fibrillary Acidic Protein; 0/Intracellular Signaling Peptides and Proteins; 20449-79-0/Melitten; 29343-52-0/4-hydroxy-2-nonenal; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Phospholipases A2; EC 4.2.1.-/Hydro-Lyases; EC 4.2.1.11/Phosphopyruvate Hydratase; EC 4.2.1.54/lactate dehydratase
Comments/Corrections
Comment In:
Ann Neurol. 2006 Apr;59(4):577-9   [PMID:  16566026 ]

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