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Topical application of dynorphin A (1-17) antibodies attenuates neuronal nitric oxide synthase up-regulation, edema formation, and cell injury following focal trauma to the rat spinal cord.

Abstract
Previous investigations from our laboratory show that up-regulation of neuronal nitric oxide synthase (NOS) following spinal cord injury (SCI) is injurious to the cord. Antiserum to dynorphin A (1-17) induces marked neuroprotection in our model of SCI, indicating an interaction between dynorphin and NOS regulation. The present investigation was undertaken to find out whether topical application of dynorphin A (1-17) antiserum has some influence on neuronal NOS up-regulation in the traumatized spinal cord. SCI was produced in anesthetized animals by making a unilateral incision into the right dorsal horn of the T10-11 segments. The antiserum to dynorphin A (1-17) was applied (1 : 20, 20 microL in 10 seconds) 5 minutes after trauma over the injured spinal cord and the rats were allowed to survive 5 hours after SCI. Topical application of dynorphin A (1-17) antiserum significantly attenuated neuronal NOS up-regulation in the adjacent T9 and T12 segments. In the antiserum-treated group, spinal cord edema and cell injury were also less marked. These observations provide new evidence that the opioid active peptide dynorphin A may be involved in the mechanisms underlying NOS regulation in the spinal cord after injury, and confirms our hypothesis that up-regulation of neuronal NOS is injurious to the cord.
AuthorsH S Sharma, F Nyberg, T Gordh, P Alm
JournalActa neurochirurgica. Supplement (Acta Neurochir Suppl) Vol. 96 Pg. 309-15 ( 2006) ISSN: 0065-1419 [Print] Austria
PMID16671477 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies
  • Neuroprotective Agents
  • Dynorphins
  • Nitric Oxide Synthase Type I
Topics
  • Animals
  • Antibodies (administration & dosage, immunology)
  • Dynorphins (immunology)
  • Edema (etiology, immunology, prevention & control)
  • Male
  • Neuroprotective Agents (administration & dosage)
  • Nitric Oxide Synthase Type I (immunology)
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries (complications, drug therapy, immunology)
  • Treatment Outcome
  • Up-Regulation (drug effects)

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