Annexin A1 reduces inflammatory reaction and tissue damage through inhibition of phospholipase A2 activation in adult rats following spinal cord injury.
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.
Liu
Nai-Kui
NK
Department of Neurological Surgery Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA.
Zhang
Yi Ping
YP
Han
Shu
S
Pei
Jiong
J
Xu
Lisa Y
LY
Lu
Pei-Hua
PH
Shields
Christopher B
CB
Xu
Xiao-Ming
XM
D000818:Animals; D017305:Annexin A1 / Q000008:administration & dosage / Q000627:therapeutic use*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004594:Electrophysiology; D004789:Enzyme Activation / Q000187:drug effects; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D005260:Female; D005911:Gliosis / Q000473:pathology; D007249:Inflammation / Q000517:prevention & control*; D007278:Injections, Spinal; D009043:Motor Activity / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D013266:Stilbamidines
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D017305:Annexin A1; D013266:Stilbamidines; D009195:Peroxidase; D010741:Phospholipases A; D054467:Phospholipases A2