AI Article Synopsis

  • Pathologic opening of the blood-brain barrier can speed up the progression of neural diseases, and basigin plays a crucial role in this process as a glycosylated molecule found in endothelial cells that form the barrier.
  • The study demonstrated that different glycosylation forms of basigin (complex-type and high-mannose-type) exist in these cells, and that manipulating these forms can impact the barrier's integrity in response to harmful stimuli.
  • In experiments, blocking the expression of high-mannose-type glycan kept endothelial cell monolayers intact under stress, and in vivo tests showed that treating mice with endoglycosidase H could protect and even repair the blood-brain barrier from harmful openings.

Article Abstract

Pathologic opening of the blood-brain barrier accelerates the progression of various neural diseases. Basigin, as an essential molecule for the opening of the blood-brain barrier, is a highly glycosylated transmembrane molecule specified in barrier-forming endothelial cells. This study analyzed the involvement of basigin in the regulation of the blood-brain barrier focusing on its glycosylation forms. First, basigin was found to be expressed as cell surface molecules with complex-type glycan as well as those with high-mannose-type glycan in barrier-forming endothelial cells. Monolayers of endothelial cells with suppressed expression of basigin with high-mannose-type glycan were then prepared and exposed to pathologic stimuli. These monolayers retained their barrier-forming properties even in the presence of pathologic stimuli, although their expression of basigin with complex-type glycan was maintained. In vivo, the blood-brain barrier in mice pretreated intravenously with endoglycosidase H was protected from opening under pathologic stimuli. Pathologically opened blood-brain barrier in streptozotocin-injected mice was successfully closed by intravenous injection of endoglycosidase H. These results show that high-mannose-type glycan of the basigin molecule is essential for the opening of the blood-brain barrier and therefore a specific target for protection as well as restoration of pathologic opening of the blood-brain barrier.

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http://dx.doi.org/10.1016/j.ajpath.2023.11.007DOI Listing

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