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Indeed, HGF protects BBB disruption after microsphere embolism-induced sustained cerebral ischemia by avoiding the inhibition of Bcl-2 (Date et al., 2006), thus decreasing apoptosis, and by reducing the expression of occludin and zonula occludens (ZO)-1, which are tight junction proteins, in cerebrovascular endothelial cells (Takeo et al., 2008)

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Intriguingly, MRI evidence of BBB disruption has been noted in seemingly normal white matter even before the emergence of enhancing lesions, as well as in non-enhancing regions, implying that BBB impairment precedes both clinical symptoms and other MRI-evident changes in the disease course

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This is a particularly strong concern for peptides like BPC-157