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

Objective: To investigate whether phospholipase A(2) (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 PLA(2) 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 PLA(2) activity and cytosolic PLA(2) expression increased significantly, with cytosolic PLA2 expression being localized mainly in neurons and oligodendrocytes. Both PLA(2) and melittin, an activator of endogenous PLA(2), induced spinal neuronal death in vitro, which was substantially reversed by mepacrine, a PLA(2) inhibitor. When PLA(2) 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. hater LA increased significantly after SCI, may play a key role in mediating neuronal death and oligodendrocyte demyelination following SCI. Blocking PLA(2) action may represent a novel repair strategy to reduce tissue damage and increase function after SCI.