缺血再灌注脑水肿离子微环境时空变化规律及干预

Stroke is the first leading cause of disability and mortality in adults of China. Endovascular intervention is the most effective therapeutic approach to recanalize the occluded major intracranial artery. Timely recanalization within the time window of acute ischemic stroke can reduce the mortality and morbidity in patients by saving the cerebral penumbra around the infract core. However, for some patients, the recanalization often leads to exacerbation of interstitial brain edema, known as cerebral ischemia-reperfusion edema (CIRE). Targeting to the critical scientific problem of CIRE, the research team, as the world leader in the field of endovascular therapy for ischemic cerebrovascular disease, will establish a multi-dimensional ion microenvironment-based CIRE progress model to study the temporal and spatial profile of ionic microenvironment, and to explore the candidate interventions of CIRE. The study plan to determine the characteristics of the ionic profile of multiple cerebral interstitial sites in permanent and transient middle cerebral artery occlusion rat model (MCAO), using blood-brain dual channel microdialysis combined with inductively-coupled plasma mass spectrometry (ICP-MS) technology. The candidate interventions of CIRE, including glibenclamide treatment and controlled reperfusion, are planned to be evaluated in the multi-dimensional ion microenvironment-based CIRE progress model by comparing the differences of histology, cytology and molecule biology among the interventions. It is anticipated that the study will fully discover the temporal and spatial profile of ion microenvironment during CIRE progress, and its mechanisms in CIRE interventions.

脑卒中是我国成人首位致残和死亡原因。血管内介入治疗是开通颅底大动脉闭塞性卒中的最有效手段，及时开通闭塞血管能够挽救濒临梗死的缺血半暗带脑组织，降低脑卒中死亡率和致残率。然而，闭塞血管的再通往往带来间质性脑水肿的加重，称之为缺血再灌注脑水肿（CIRE）。项目组为国内外脑血管病介入诊疗领域领先团队，将针对CIRE这一关键科学问题，建立基于多维度离子微环境的CIRE进展模型，研究CIRE离子微环境时空变化规律及干预。研究将在永久性和不同缺血时间的短暂性大脑中动脉闭塞大鼠模型上，采用血脑双通道微透析联合电感耦合等离子体质谱技术，对CIRE离子微环境实施多位点连续动态观察，同时结合药物治疗和再灌注治疗后脑组织病理损伤、脑梗死体积、脑水肿程度和血脑屏障损伤进行组间差异评估，全面揭示离子微环境在CIRE进展中的时空变化规律，阐明基于离子微环境的CIRE干预模式的理论依据及其作用机制。

脑卒中是我国成人首位致残和死亡原因。血管内介入治疗是开通颅底大动脉闭塞性卒中的最有效手段，及时开通闭塞血管能够挽救濒临梗死的缺血半暗带脑组织，降低脑卒中死亡率和致残率。然而，闭塞血管的再通往往带来间质性脑水肿的加重，称之为缺血再灌注脑水肿（CIRE）。 本研究聚焦CIRE这一关键科学问题，首先建立基于多维度离子微环境的CIRE进展模型，研究CIRE离子微环境时空变化血脑双通道微透析联合电感耦合等离子体质谱技术，对CIRE离子微环境实施多位点连续动态观察，同时对格列本脲治疗再通后脑组织病理损伤、脑梗死体积、脑水肿程度和血脑屏障损伤进行组间差异评估，全面揭示离子微环境在CIRE进展中的时空变化规律，阐明基于离子微环境的CIRE干预模式的理论依据及其作用机制；其次，本研究开展了渐增式血流重建模式对MCAO大鼠脑组织的中、长期保护作用机制研究，揭示了GFR的脑保护作用及分子机制；第三，本研究开展了急性脑卒中血管内治疗后早期神经功能恶化的循证医学研究，发现了END发生的风险因素，对于临床工作中术前筛选病人、评估预后风险及围手术期管理具有较好的指导意义。