Cytosolic phospholipase A2 protein as a novel therapeutic target for spinal cord injury

Nai Kui Liu, Ling Xiao Deng, Yi Ping Zhang, Qing Bo Lu, Xiao Fei Wang, Jian Guo Hu, Eddie Oakes, Joseph V. Bonventre, Christopher B. Shields, Xiao Ming Xu

Research output: Contribution to journalArticle

42 Scopus citations


Objective The objective of this study was to investigate whether cytosolic phospholipase A2 (cPLA2), an important isoform of PLA 2 that mediates the release of arachidonic acid, plays a role in the pathogenesis of spinal cord injury (SCI). Methods A combination of molecular, histological, immunohistochemical, and behavioral assessments were used to test whether blocking cPLA2 activation pharmacologically or genetically reduced cell death, protected spinal cord tissue, and improved behavioral recovery after a contusive SCI performed at the 10th thoracic level in adult mice. Results SCI significantly increased cPLA2 expression and activation. Activated cPLA2 was localized mainly in neurons and oligodendrocytes. Notably, the SCI-induced cPLA2 activation was mediated by the extracellular signal-regulated kinase signaling pathway. In vitro, activation of cPLA2 by ceramide-1-phosphate or A23187 induced spinal neuronal death, which was substantially reversed by arachidonyl trifluoromethyl ketone, a cPLA2 inhibitor. Remarkably, blocking cPLA2 pharmacologically at 30 minutes postinjury or genetically deleting cPLA2 in mice ameliorated motor deficits, and reduced cell loss and tissue damage after SCI. Interpretation cPLA2 may play a key role in the pathogenesis of SCI, at least in the C57BL/6 mouse, and as such could be an attractive therapeutic target for ameliorating secondary tissue damage and promoting recovery of function after SCI.

Original languageEnglish (US)
Pages (from-to)644-658
Number of pages15
JournalAnnals of Neurology
Issue number5
StatePublished - May 2014

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Liu, N. K., Deng, L. X., Zhang, Y. P., Lu, Q. B., Wang, X. F., Hu, J. G., Oakes, E., Bonventre, J. V., Shields, C. B., & Xu, X. M. (2014). Cytosolic phospholipase A2 protein as a novel therapeutic target for spinal cord injury. Annals of Neurology, 75(5), 644-658.