Development of long-term survival spinal cord ischemia model in mice

Abstract

Objective To develop long-term survival spinal cord ischemia model mimicking the injury from the surgery of thoracoabdominal aneurysm in mice.Methods Thoracic aorta was clamped for 8,10 and 12 min via left lateral thoracotomy.The mice subject to sham operation served as control group.The lumbar spinal cord blood flow was measured during thoracic aorta cross-clamping.Hind limbs movement function was evaluated before and 1 h,1,3,5,7 days,and 2,4 weeks post-injury.The slices of the spinal cord were observed and survival neurons in the ventral horn were evaluated at 7th day post-injury.Survival curve was analyzed at 4th week post-injury in mice.The data were statistically analyzed using SPSS 17.0 software.Results The blood flow was reduced to (7.2 ± 3.5) ％ of the baseline after crossclamping the thoracic aorta.There was no hind limbs movement functional deficit,and histological staining of the spinal cord ischemia slices was normal in the control group.There was a most serious hind limbs movement functional deficit at 1 st h post-injury.The duration of 8 min cross-clamping could result in movement functional deficit,but open field Basso Beattie Bresnahan (BBB) score recovered at 2nd week postinjury (P ＞ 0.05 vs.control group).The duration of 10 min cross-clamping could result in continuous and stable hind limbs movement functional deficit at 4th week (P ＜0.01 vs.control group for open field BBB score and latency to fall from Rota rod) and neuronal cell death (P ＜ 0.01 vs.control group for the ventral horn neurons).Most importantly,the mice had a long term survival in 10 min group (the median survival period was 24.7 days,P ＞0.05 vs.8 min group).The duration of 12 min cross-clamping could result in less probability of long-term survival (the median survival period was 14.7 days,P ＜0.01 vs.8 min group and 10 min group),although it could result in serious hind limbs movement functional deficit.Conclusion Ten min was the best duration for mice spinal cord ischemia model through thoracic aorta cross-clamping.This kind of model can be used to study the dynamic changes of spinal cord ischemia because of the animals' long-term survival. Key words: Spinal cord ischemia; Model,animal; Mouse; Long-term survival