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

Nai Kui Liu, Yi Ping Zhang, William Lee Titsworth, Xiaoyan Jiang, Shu Han, Pei Hua Lu, Christopher B. Shields, Xiao Ming Xu

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

Objective: To investigate whether phospholipase A2 (PLA 2) 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 PLA 2 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 PLA1 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 PLA 2-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.

Original languageEnglish (US)
Pages (from-to)606-619
Number of pages14
JournalAnnals of Neurology
Volume59
Issue number4
DOIs
StatePublished - Apr 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Liu, N. K., Zhang, Y. P., Titsworth, W. L., Jiang, X., Han, S., Lu, P. H., Shields, C. B., & Xu, X. M. (2006). A novel role of phospholipase A2 in mediating spinal cord secondary injury. Annals of Neurology, 59(4), 606-619. https://doi.org/10.1002/ana.20798