Effect of PJ34 on Spinal Cord Tissue Viability and Gene Expression in a Murine Model of Thoracic Aortic Reperfusion Injury

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.