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

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.

Keywords

paralysis ischemia reperfusion injury poly ADP-ribose polymerase inflammation

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