A novel role of phospholipase A2 in mediating spinal cord secondary injury

Authors

  • Nai-Kui Liu MD, PhD,

    1. Departments of Neurological Surgery and Anatomical Sciences and Neurobiology, Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, KY
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  • Yi Ping Zhang MD,

    1. Departments of Neurological Surgery and Anatomical Sciences and Neurobiology, Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, KY
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  • William Lee Titsworth BS,

    1. Departments of Neurological Surgery and Anatomical Sciences and Neurobiology, Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, KY
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  • Xiaoyan Jiang MD,

    1. Department of Neurobiology, Shanghai Second Medical University, Shanghai, China
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  • Shu Han PhD,

    1. Department of Neurobiology, Shanghai Second Medical University, Shanghai, China
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  • Pei-Hua Lu MD,

    1. Department of Neurobiology, Shanghai Second Medical University, Shanghai, China
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  • Christopher B. Shields MD,

    1. Departments of Neurological Surgery and Anatomical Sciences and Neurobiology, Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, KY
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  • Xiao-Ming Xu PhD

    Corresponding author
    1. Departments of Neurological Surgery and Anatomical Sciences and Neurobiology, Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, KY
    2. Department of Neurobiology, Shanghai Second Medical University, Shanghai, China
    • Department of Neurological Surgery, University of Louisville School of Medicine, 511 S. Floyd Street, MDR 616, Louisville, KY 40292
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Abstract

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. Ann Neurol 2006

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