The Research Of Recanalization Time In Carotid Stenosis Complicating Multiple Cerebral Embolisms In Rats

Objective To establish and evaluate the model of carotid artery severe stenosis complicating multiple cerebral embolisms in rats.To observe the express of EPO and MMP-9 in different time and to find an optimal time of CCA recanalized in rats with CCA stenosis complicating multiple cerebral embolism.Methods The experiment procedure consisted of 2parts,model establishing and the study group.130 SD rats were divided into 2 groups for random.The model group (n=51),which were divided into 3 sub-groups:ultrasound group(n=26),TTC stain group(n=10)and neurological behavioral evaluation group(n=15).The study group included 2 big groups:CCA stenosis group(n=24),CCA stenosis recanalization group (n=24).The two groups were further divided into six sub-groups respectively for different time to open CCA stenosis and sacrifice.The CCA severe stenosis was induced by ligation of common carotid artery using a needle to control the degree of stenosis.Cerebral embolism was induced by injecting the autogeneic embolus.The color Doppler flow imaging(CDFI)was used to detect the degree of CCA stenosis; TTC staining was used to determine the infarction volume.The changes of regional cerebral blood flow(rCBF)were continuously measured by laser-Doppler flow meter. Four kinds of neurological behavioral evaluation tests were used to evaluate the neurologic impairments.The expressions of EPO and MMP-9 were detected by method of immunohistochemistry.ResultsPhysiological variables:Physiological variables were generally stabilization before and after surgery in every group. CDFI:In sham-operated group,the images displayed the vessel of CCA,ICA clearly.The vessel wall was smooth and uniformity.In CCA stenosis group,the residue of CCA diameter was 0.18±0.06mm,PSV was 256.92±81.34cm/s which was significantly higher than sham-operated group.The CDFI displayed that the stenosis of CCA achieved 70%in CCA stenosis complicating multiple cerebral embolism group.There was no markedly difference between pre-embolism and post-embolism (p＞0.05).The change of hemorheology parameters reached severe narrow in these 2 groups and the parameters were significantly difference than the group of sham-operated(p＜0.05).TTC staining and infarction:Multiple infarctions were found by TTC staining, scatterings in different regions.The infarction volum was(23.68±19.32)mm~3.Hemorrhage rate:The hemorrhage rates increased in 5d and in carotid stenosis group.It decreased after 7d and 14d in 2 groups.Measurement of MMP-9:The expression of MMP-9 in ischemia hemisphere were significantly higher compared with non-ischemic hemisphere(p＜0.05).In CCA stenosis group,MMP-9 increased significantly in 1d,the second peak was in 5d,until 7d it decreased lowest.In recanalized group,the expressions were increased in 5d and achieved peak.It decreased in 7d too.Measurement of EPO:The expression of EPO in ischemia hemisphere were significantly higher(p＜0.05)compared with non-ischemic hemisphere.The expression of EPO in carotid stenosis group,in the 3d EPO increased,at the peak in 5d,until 7d it decreased lowest.In CCA stenosis recanalization group,the expressions were increased from 5d and achieved peak in 7d.Compared with CCA stenosis group, the expression increased markedly in recanalization group in 7d(p＜0.05).Conclusions1.The reversibility model of CCA stenosis complicating cerebral embolism is reproducible and easy to be operated.It could simulate the carotid stenosis in clinic, so we could use this model for research of the angioplasty.2.As a substance relating with destroying the blood brain barrier and inducing the hemorrhage after thrombolysis,the expression of MMP-9 was increased in 5d and it decreased after 7d in 2 groups.3.As a neuroprotective effect factor in cerebral ischemia,the expression of EPO in 7d in recanalized group was in maximum,and it may be produce the protection to ischemia after CCA stenosis being recanalized.4.Opened carotid stenosis in 7d produced higher EPO and lower MMP-9.Our study suggested that the optimal time to open the CCA stenosis complicating cerebral embolism is 7d and after 7d.