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

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.

journal_name

Ann Neurol

journal_title

Annals of neurology

authors

Liu NK,Zhang YP,Titsworth WL,Jiang X,Han S,Lu PH,Shields CB,Xu XM

doi

10.1002/ana.20798

keywords:

subject

Has Abstract

pub_date

2006-04-01 00:00:00

pages

606-19

issue

4

eissn

0364-5134

issn

1531-8249

journal_volume

59

pub_type

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