Annexin A1 reduces inflammatory reaction and tissue damage through inhibition of phospholipase A2 activation in adult rats following spinal cord injury

Nai Kui Liu, Yi Ping Zhang, Shu Han, Jiong Pei, Lisa Y. Xu, Pei Hua Lu, Christopher B. Shields, Xiao Ming Xu

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Annexin A1 (ANXA1) has been suggested to be a mediator of the anti-inflammatory actions of glucocorticoids and more recently an endogenous neuroprotective agent. In the present study, we investigated the anti-inflammatory and neuroprotective effects of ANXA1 in a model of contusive spinal cord injury (SCI). Here we report that injections of ANXA1 (Ac 2-26) into the acutely injured spinal cord at 2 concentrations (5 and 20 μg) inhibited SCI-induced increases in phospholipase A2 and myeloperoxidase activities. In addition, ANXA1 administration reduced the expression of interleukin-1β and activated caspase-3 at 24 hours, and glial fibrillary acidic protein at 4 weeks postinjury. Furthermore, ANXA1 administration significantly reversed phospholipase A2-induced spinal cord neuronal death in vitro and reduced tissue damage and increased white matter sparing in vivo, compared to the vehicle-treated controls. Fluorogold retrograde tracing showed that ANXA1 administration protected axons of long descending pathways at 6 weeks post-SCI. ANXA1 administration also significantly increased the number of animals that responded to transcranial magnetic motor-evoked potentials. However, no measurable behavioral improvement was found after these treatments. These results, particularly the improvements obtained in tissue sparing and electrophysiologic measures, suggest a neuroprotective effect of ANXA1.

Original languageEnglish (US)
Pages (from-to)932-943
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume66
Issue number10
DOIs
StatePublished - Oct 1 2007

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Keywords

  • Annexin A1
  • Inflammation
  • Neuroprotection
  • Phospholipase A
  • Spinal cord injury

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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