Effect of PJ34 on spinal cord tissue viability and gene expression in a murine model of thoracic aortic reperfusion injury.
BACKGROUND
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.
Stone
David H
DH
Division of Vascular and Endovascular Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Conrad
Mark F
MF
Albadawi
Hassan
H
Entabi
Fateh
F
Stoner
Michael C
MC
Cambria
Richard P
RP
Watkins
Michael T
MT
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000235:genetics*; D020869:Gene Expression Profiling; D006614:Hindlimb / Q000098:blood supply / Q000294:innervation; D008026:Ligation; D008124:Locomotion; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010616:Phenanthrenes / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D013116:Spinal Cord / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D014022:Tissue Survival / Q000187:drug effects
C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger; D051546:Cyclooxygenase 2