Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Graduate Program in Neuroscience, University of Michigan Medical School, Ann Arbor, MI, USA.
Methods Mol Biol. 2022;2492:289-305. doi: 10.1007/978-1-0716-2289-6_17.
Cerebral ischemic injury evokes a complex cascade of pathophysiological events at the blood-vascular-parenchymal interface. These evolve over time and space and result in progressive neurological damage. Emerging evidence suggests that blood-brain barrier (BBB) recovery and reestablishment of BBB impermeability are incomplete and that these could influence stroke injury recovery, increase the risk of new stroke occurrence, and be a solid substrate for developing vascular dementia. Recent work from the author's laboratory has established the existence of incomplete BBB recovery in chronic stroke conditions that was induced by structural alterations to brain endothelial junctional complexes and persistent BBB leakage. The experimental methodology presented here is focused on modelling chronic stroke injury using an in vivo thromboembolic mouse stroke model and how to evaluate the kinetics and magnitude of BBB hyperpermeability in chronic stroke conditions using a combination of magnetic resonance imaging, tracer studies, and immunohistochemistry.
脑缺血损伤在血-血管-实质界面引发一系列复杂的病理生理事件。这些事件随着时间和空间的推移而演变，并导致进行性神经损伤。新出现的证据表明，血脑屏障（BBB）的恢复和 BBB 通透性的重建是不完全的，这可能会影响中风损伤的恢复，增加新中风发生的风险，并为血管性痴呆的发展提供坚实的基础。作者实验室的最新研究已经证实，在由脑内皮细胞连接复合体结构改变和持续的 BBB 渗漏引起的慢性中风情况下，存在不完全的 BBB 恢复。这里介绍的实验方法侧重于使用体内血栓栓塞性小鼠中风模型来模拟慢性中风损伤，以及如何使用磁共振成像、示踪研究和免疫组织化学相结合的方法来评估慢性中风情况下 BBB 高通透性的动力学和幅度。
