A novel role of phospholipase A2 in mediating spinal cord secondary injury
Version of Record online: 23 FEB 2006
Copyright © 2006 American Neurological Association
Annals of Neurology
Volume 59, Issue 4, pages 606–619, April 2006
How to Cite
Liu, N.-K., Zhang, Y. P., Titsworth, W. L., Jiang, X., Han, S., Lu, P.-H., Shields, C. B. and Xu, X.-M. (2006), A novel role of phospholipase A2 in mediating spinal cord secondary injury. Ann Neurol., 59: 606–619. doi: 10.1002/ana.20798
- Issue online: 24 MAR 2006
- Version of Record online: 23 FEB 2006
- Manuscript Accepted: 13 DEC 2005
- Manuscript Revised: 12 DEC 2005
- Manuscript Received: 19 JUL 2005
- NIH. Grant Numbers: NS36350, NS52290
- Kentucky Spinal Cord and Head Injury Research Trust. Grant Number: 416
- Daniel Heumann Fund for Spinal Cord Research
- Paralysis Project of America. Grant Number: GRNT050293
To investigate whether phospholipase A2 (PLA2) plays a role in the pathogenesis of spinal cord injury (SCI).
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.
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.
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