异常血管新生影响糖尿病患者缺血性脑卒中预后的磁共振成像研究

Diabetes is an independent factor for the poor prognosis after ischemic stroke, but the cause is not clear. Angiogenesis plays a role in promoting functional recovery and it includes the dynamic changes in blood-brain barrier (BBB) permeability, blood perfusion and vessel density. The BBB permeability is a key process which appears increased at the early stage and then gradually returns to the normal level. However, diabetes can cause abnormal angiogenesis, such as the findings of increased BBB injury from our study and increased/decreased vascular density from other studies. In addition, we found that BBB injury is an independent risk factor for poor prognosis after ischemic stroke in diabetic patients. Therefore, we speculate that BBB injury caused by diabetes in the early stage of angiogenesis would lead to neovascularization with abnormal structure and function in the late stage, which may result in poor outcome after ischemic stroke. This project plans to study the dynamic changes of angiogenesis at the peri-infarct regions using multi-sequence MR techniques (including DCE, VSI, ASL, IVIM) in patients with diabetes and without diabetes. We aim to understand the relationship between abnormal angiogenesis caused by diabetes and prognosis after ischemic stroke in diabetic patients. If our project would be successful, it can provide a theoretical basis for improving the prognosis of stroke in diabetic patients with angiogenesis as a therapeutic target in future.

糖尿病是缺血性脑卒中预后差的独立影响因素，但原因尚不明确。血管新生具有促进神经功能恢复的作用，它包括血脑屏障通透性、血流灌注及血管密度的动态变化，其中血脑屏障通透性由增加逐渐恢复至正常水平是关键过程。然而，糖尿病会引起异常血管新生，例如我们前期发现糖尿病增加血脑屏障损伤和其他研究报道糖尿病引起血管密度增加/减少。我们还发现血脑屏障损伤是糖尿病患者缺血性脑卒中预后差的独立影响因素。因此，我们推测糖尿病可能通过损伤血管新生早期的血脑屏障，引起后期结构和功能异常的新生血管，从而不利于缺血性脑卒中的预后。本项目拟采用多序列磁共振技术（包括DCE、VSI、ASL、IVIM）研究糖尿病与非糖尿病患者的缺血性脑卒中病灶边缘血管新生的动态变化，明确糖尿病引起的异常血管新生与糖尿病患者缺血性脑卒中预后的关系。本项目的研究如能成功，能为将来以血管新生作为治疗靶点改善糖尿病患者的脑卒中预后提供理论依据。

糖尿病是缺血性脑卒中预后差的独立影响因素，但原因尚不明确。本项目基于多模式磁共振技术研究了糖尿病相关的类淋巴循环障碍在缺血性脑卒中预后中的作用，发现以下结果：（1）糖尿病患者常合并有脑小血管病的影像学表现（包括白质高信号、腔隙性梗死），而且与脑卒中预后差有关；糖尿病会造成脑小血管病患者全脑水平的血管搏动和脑脊液流入耦合显著下降，提示类淋巴循环障碍可能与糖尿病脑卒中预后有关。（2）在脑卒中急性期，梗死病灶会造成远隔相连的皮质脊髓束损伤，这种损伤与患者神经功能缺失严重程度显著相关；在脑卒中慢性期，梗死病灶会通过相连的白质造成远隔中央前回萎缩，并且皮层萎缩与神经突退变有关。（3）在Notch3基因突变的脑小血管病中，白质退变会随着白质水肿增加而逐渐加重，而且白质水肿是腔隙性梗死、微出血的独立影响因素，提示白质水肿是白质损伤的早期环节；在散发性脑小血管病中，血管周围间隙扩大与邻近白质组织液积聚有关，提示类淋巴循环障碍参与白质水肿的形成；在社区人群中，糖尿病与白质血管周围间隙扩大显著相关，支持糖尿病与类淋巴循环障碍有关。因此，我们提出糖尿病可能通过类淋巴循环障碍导致白质损伤，从而影响脑卒中的康复过程，这为后续深入研究奠定了工作基础。