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

J Neuropathol Exp Neurol. 2007 Oct;66(10):932-43. doi: 10.1097/nen.0b013e3181567d59.

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 microg) inhibited SCI-induced increases in phospholipase A2 and myeloperoxidase activities. In addition, ANXA1 administration reduced the expression of interleukin-1beta 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A1 / administration & dosage
  • Annexin A1 / therapeutic use*
  • Blotting, Western
  • Cell Survival / drug effects
  • Cells, Cultured
  • Electrophysiology
  • Enzyme Activation / drug effects
  • Evoked Potentials, Motor / drug effects
  • Evoked Potentials, Motor / physiology
  • Female
  • Gliosis / pathology
  • Inflammation / prevention & control*
  • Injections, Spinal
  • Motor Activity / drug effects
  • Peroxidase / metabolism
  • Phospholipases A / metabolism*
  • Phospholipases A2
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / enzymology
  • Spinal Cord / pathology
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / enzymology*
  • Spinal Cord Injuries / pathology
  • Stilbamidines

Substances

  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • Annexin A1
  • Stilbamidines
  • Peroxidase
  • Phospholipases A
  • Phospholipases A2