A mouse model of ischemic spinal cord injury with delayed paralysis caused by aortic cross-clamping

Abstract

Background: Spinal cord ischemia and paralysis are devastating perioperative complications that can accompany open or endovascular repair surgery for aortic aneurysms. Here, we report on the development of a new mouse model of spinal cord ischemia with delayed paralysis induced by cross-clamping the descending aorta. Methods: Transient aortic occlusion was produced in mice by cross-clamping the descending aorta through a lateral thoracotomy. To establish an optimal surgical procedure with limited mortality, variable cross-clamp times and core temperatures were tested between experiments. Results: The onset of paresis or paralysis and postsurgical mortality varied as a function of cross-clamp time and core temperature that was maintained during the period of crossclamp. Using optimal surgical parameters (7.5-min crossclamp duration at 33°C core temperature), the onset of paralysis is delayed 24-36 h after reperfusion, and more than 95% of mice survive through 9 weeks after surgery. These mice are further stratified into two groups, 70% (nβ19/27) of mice developing severe hind limb paralysis and the remaining mice showing mild, though still permanent, behavioral deficits. Conclusion: This new model should prove useful as a preclinical tool for screening neuroprotective therapeutics and for defining the basic biologic mechanisms that cause delayed paralysis and neurodegeneration after transient spinal cord ischemia. Copyright © 2010.