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


CONCLUSIONS
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.
Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Nai-Kui
NK
Liu
Yi Ping
YP
Zhang
William Lee
WL
Titsworth
Xiaoyan
X
Jiang
Shu
S
Han
Pei-Hua
PH
Lu
Christopher B
CB
Shields
Xiao-Ming
XM
Xu
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D039481:CD11b Antigen / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006836:Hydro-Lyases / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008555:Melitten / Q000008:administration & dosage; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D010741:Phospholipases A / Q000008:administration & dosage / Q000502:physiology*; D054467:Phospholipases A2; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D013997:Time Factors
D000447:Aldehydes; D039481:CD11b Antigen; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D047908:Intracellular Signaling Peptides and Proteins; D008555:Melitten; D010741:Phospholipases A; D054467:Phospholipases A2; D006836:Hydro-Lyases; D010751:Phosphopyruvate Hydratase; C045581:lactate dehydratase; C027576:4-hydroxy-2-nonenal