Spinal cord ischemia - Development of a model in the mouse

Background and Purpose-Spinal cord ischemia with resulting paraplegia is a devastating complication of thoracoabdominal aortic surgery. Experimental m odels of spinal cord ischemia have been developed in primate, dog, pig, rab bit, and rat with variable reproducibility, but none has been developed in mouse. Because genetically engineered mice have become important to examine the impact of specific genes in ischemic pathophysiology, we sought to dev elop a reproducible mouse model of spinal cord ischemia. Methods-C57BL/6NCrlBR mice were subjected to cross-clamping of the aortic a rch, left subclavian artery, and internal mammary artery for 9 minutes (gro up A; n=8) or 11 minutes (group B; n=29) followed by reperfusion for 24 or 48 hours. Mean distal arterial blood pressure (left femoral artery) and lum bar (L1) spinal cord blood flow (laser-Doppler flowmetry) were measured for the duration of the procedure. The arterial blood supply of the spinal cor d was visualized by intravascular perfusion of carbon black ink. We evaluat ed motor function in the hind limbs at 0, 1, 3, 6, and 24 hours after reper fusion using a rating scale of 0 (normal function) to 6 (total absence of m ovement). Spinal cord histopathology was evaluated after 24 and 48 hours of reperfusion by Luxol fast blue-hematoxylin and eosin. Results-The vascular anatomy of the mouse and human spinal cord appeared si milar in that blood was supplied by I anterior and 2 posterior spinal arter ies and heterosegmental radicular arteries. During combined occlusion of ao rtic arch and left subclavian artery, mean distal arterial blood pressure d ropped to 10+/-5 mm Hg, and spinal cord blood flow at the L1 level decrease d to 27+/-7% of baseline. All animals recovered from anesthesia with acute paraplegia, Animals in the 9-minute group (group A) showed steady recovery of hind Limb function over the ensuing 24 hours, whereas the majority (80%) in the 11-minute group (group B) remained paralyzed with maximum deficit t hroughout the postoperative period. Mortality was 0% and 21% in groups A an d B, respectively. Maximal ischemic damage was observed at the lower thorac ic and higher lumbar spinal levels in both groups. In group A (9 minutes), tissue damage was mild, affecting predominantly dorsal horns and intermedia te gray matter, whereas ventral horns were minimally involved. All mice in group B (11 minutes) showed extensive gray matter lesions particularly invo lving dorsal horns and intermediate areas; in ventral horns, >50% of motor neurons died. White matter lesions were present in the most severely damage d cords only. Conclusions-Spinal cord ischemia caused by aortic arch plus left subclavian artery cross-clamping provides a mouse model useful for the study of spina l cord injury and of potential relevance to the complications following tho racoabdominal aortic surgery in humans.