Effect of PJ34 on spinal cord tissue viability and gene expression in a murine model of thoracic aortic reperfusion injury

Vasc Endovascular Surg. 2009 Oct-Nov;43(5):444-51. doi: 10.1177/1538574409333582. Epub 2009 Jul 29.

Abstract

Introduction: These studies were designed to determine whether PJ34, a novel Poly-ADP Ribose Polymerase Inhibitor, modulates expression of markers of stress and inflammation in the spinal cord following ischemia/ reperfusion(TAR).

Methods: 129S1/SvImj mice were subjected to thoracic aortic occlusion and 48 hours of reperfusion (n = 38). EXPERIMENTAL GROUPS INCLUDED: Untreated Control (UC, n = 21); PJ34 (PJ34, n = 11) and sham (S, n = 6). At 48 hours, mice were euthanized for mRNA analysis and assessment of spinal cord viability.

Results: PJ34 improved spinal cord tissue viability following TAR (UC:53.1 +/- 6.3, PJ34:73.5 +/- 4.1% sham, p < 0.01). mRNA analysis revealed significant expression of stress response genes in UC and PJ34 treated mice.

Conclusions: PJ34 enhanced mitochondrial activity and preserved neurologic function following TAR despite the expression of stress and pro-inflammatory markers within the spinal cord. The ongoing cord stress response in neurologically intact PJ34 treated mice may indicate the potential to develop delayed neurologic dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / physiology
  • Cyclooxygenase 2 / genetics*
  • Gene Expression Profiling
  • Hindlimb / blood supply
  • Hindlimb / innervation
  • Ligation
  • Locomotion
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mitochondria / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phenanthrenes / pharmacology*
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • RNA, Messenger / metabolism
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / pathology*
  • Reperfusion Injury / physiopathology
  • Spinal Cord / blood supply
  • Spinal Cord / metabolism
  • Spinal Cord / pathology*
  • Tissue Survival / drug effects

Substances

  • N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
  • Phenanthrenes
  • Poly(ADP-ribose) Polymerase Inhibitors
  • RNA, Messenger
  • Cyclooxygenase 2