A novel role of phospholipase A sub(2) in mediating spinal cord secondary injury

Objective: To investigate whether phospholipase A sub(2) (PLA sub(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 sub(2) activity, expression, and cellular localization after a contusive SCI; and (2) the effects of exogenous PLA sub(2) on spinal cord neuronal death in vitro and tissue damage, inflammation, and function in vivo. Results: After SCI, both PLA sub(2) activity and cytosolic PLA sub(2) expression increased significantly, with cytosolic PLA sub(2) expression being localized mainly in neurons and oligodendrocytes. Both PLA sub(2) and melittin, an activator of endogenous PLA sub(2), induced spinal neuronal death in vitro, which was substantially reversed by mepacrine, a PLA sub(2) inhibitor. When PLA sub(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 sub(2)-induced demyelination was significantly reversed by mepacrine. Interpretation: PLA sub(2), increased significantly after SCI, may play a key role in mediating neuronal death and oligodendrocyte demyelination following SCI. Blocking PLA sub(2) action may represent a novel repair strategy to reduce tissue damage and increase function after SCI. Ann Neurol 2006