Applications Of Synchrotron Radiation Angiography In Experimental Rodent Stroke

Stroke is one of the leading causes of death with high morbidity,mortality and disability rate in China. Rodent suture middle cerebral artery occlusion(MCAO) model is the most widely used to mimic human ischemic stroke. However, many factors may affect the blood flow and infarct volume, and animal survival after middle cerebral artery occlusion. Therefore, imaging the cerebral circulation in high resolution in living animal during brain ischemia may contribute to the researching progress in pathology of stroke and model stability. Collateral circulation, which normally open after ischemic stroke, can be related to the recovery of patient. Rapamycin have the potential to improve the collateral opening after ischemic stroke. In the present study, we developed the synchrotron radiation angiography(SRA), combined with in vivo laser speckle imaging and magnetic resonance imaging, and in vitro tissue histological stainings to study the following five aspects.1. Synchrotron radiation angiography indicated that the collateral circulation from the pterygopalatine artery compensated the blood flow of the external carotid artery territory after suture middle cerebral artery occlusion with the external carotid artery transection, and then prevented masticatory muscle impairment. This result directly demonstrated that the loss of weight was not due to the external carotid artery transection.2. Synchrotron radiation angiography showed that the ophthalmic anastomoses, collaterals between the branches of the internal carotid artery and the ophthalmic artery, anastomoses between the branches of the internal carotid artery and the pterygopalatine artery were open after transient middle cerebral artery occlusion in rats. Further, we confirmed that there have no collateral between the branches of the pterygopalatine artery and the middle cerebral artery, but only have collateral between the branches of the pterygopalatine artery and endocranium after permanent middle cerebral artery occlusion in rats, suggesting that the reservation or ligation of the pterygopalatine artery did not affect the stability of infarct volume.3. Suture-induced endovascular thrombosis was a critical element affecting the success of reperfusion. Appropriate heparin treatment could improve reproducibility of mice transient middle cerebral artery occlusion model.4. We developed a novel functional synchrotron radiation angiography(fSRA) technique based on spatio-temporal analysis of contrast density. With functional synchrotron radiation angiography, we found that the vascular elasticity of the lenticulostriate arteries decreased from day 1 to day 7, and recovered from day 7 to day 28 compared to the control after transient middle cerebral artery occlusion in rats, which was parallel with brain edema formation and inversely correlated with the lenticulostriate arteries’ blood flow velocity. These results demonstrated that the change of vascular elasticity might relate to the severity of brain edema and the velocity of focal blood flow after ischemic stroke.5. Rapamycin treatment could maintain the collateral opening and improve the blood flow velocity of the pial anastomoses after transient middle cerebral artery occlusion in mice. We also found that rapamycin treatment could expand the diameter of the collateral between the posterior cerebral artery and the middle cerebral artery, and then increase the blood flow in the middle cerebral artery territory after embolic occlusion in rats. These results suggested that rapamycin treatment have a neuroprotective ability through improving collateral circulation opening.The results we obtained in these study could effectively promote the development and application of synchrotron radiation angiography technique in basic stroke research and clinical application.