University of Michigan, Ann Arbor, MI 48104, USA.
Northwestern University, Evanston, IL 60208, USA.
Cells. 2020 Sep 11;9(9):2075. doi: 10.3390/cells9092075.
Stroke is a life-threatening disease that leads to mortality, with survivors subjected to long-term disability. Microvascular damage is implicated as a key pathological feature, as well as a therapeutic target for stroke. In this review, we present evidence detailing subacute diaschisis in a focal ischemic stroke rat model with a focus on blood-brain barrier (BBB) integrity and related pathogenic processes in contralateral brain areas. Additionally, we discuss BBB competence in chronic diaschisis in a similar rat stroke model, highlighting the pathological changes in contralateral brain areas that indicate progressive morphological brain disturbances overtime after stroke onset. With diaschisis closely approximating stroke onset and progression, it stands as a treatment of interest for stroke. Indeed, the use of stem cell transplantation for the repair of microvascular damage has been investigated, demonstrating that bone marrow stem cells intravenously transplanted into rats 48 h post-stroke survive and integrate into the microvasculature. Ultrastructural analysis of transplanted stroke brains reveals that microvessels display a near-normal morphology of endothelial cells and their mitochondria. Cell-based therapeutics represent a new mechanism in BBB and microvascular repair for stroke.
中风是一种危及生命的疾病，可导致死亡，幸存者则长期残疾。微血管损伤被认为是关键的病理特征，也是中风的治疗靶点。在这篇综述中，我们提供了详细的证据，说明了局灶性缺血性中风大鼠模型中的亚急性期隔室化现象，重点关注血脑屏障（BBB）的完整性以及对侧大脑区域的相关发病过程。此外，我们还讨论了类似的大鼠中风模型中慢性隔室化的 BBB 能力，强调了对侧大脑区域的病理变化，这些变化表明中风发作后随时间推移出现进行性的形态学脑紊乱。由于隔室化与中风的发作和进展非常接近，因此它成为中风治疗的一个关注点。事实上，已经研究了使用干细胞移植来修复微血管损伤，结果表明，中风后 48 小时静脉内移植到大鼠体内的骨髓干细胞可以存活并整合到微血管中。对移植的中风大脑进行超微结构分析显示，微血管的内皮细胞及其线粒体形态接近正常。基于细胞的治疗为中风的 BBB 和微血管修复提供了新的机制。
