Journal
JOURNAL OF CLINICAL MEDICINE
Volume 10, Issue 17, Pages -Publisher
MDPI
DOI: 10.3390/jcm10173795
Keywords
transcytosis; caveolae; blood-brain barrier; ischemic stroke
Categories
Funding
- National Natural Science Foundation of China [81704019]
- American Heart Association [833696]
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Disruption of the blood-brain barrier following ischemic stroke can lead to various complications, with recent studies showing a stepwise impairment of the transcellular barrier followed by the paracellular barrier as a potential cause. Increased endothelial transcytosis, which is caveolae-mediated, has been identified as a factor independent of tight junction disintegration, challenging previous beliefs and providing new insights for future research and treatment strategies.
Blood-brain barrier (BBB) disruption following ischemic stroke (IS) contributes to hemorrhagic transformation, brain edema, increased neural dysfunction, secondary injury, and mortality. Brain endothelial cells form a para and transcellular barrier to most blood-borne solutes via tight junctions (TJs) and rare transcytotic vesicles. The prevailing view attributes the destruction of TJs to the resulting BBB damage following IS. Recent studies define a stepwise impairment of the transcellular barrier followed by the paracellular barrier which accounts for the BBB leakage in IS. The increased endothelial transcytosis that has been proven to be caveolae-mediated, precedes and is independent of TJs disintegration. Thus, our understanding of post stroke BBB deficits needs to be revised. These recent findings could provide a conceptual basis for the development of alternative treatment strategies. Presently, our concept of how BBB endothelial transcytosis develops is incomplete, and treatment options remain limited. This review summarizes the cellular structure and biological classification of endothelial transcytosis at the BBB and reviews related molecular mechanisms. Meanwhile, relevant transcytosis-targeted therapeutic strategies for IS and research entry points are prospected.
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