期刊
NEUROSCIENCE LETTERS
卷 715, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2019.134594
关键词
Blood-Brain barrier; Brain endothelial cells; Oligodendrocytes; Oligodendrocyte progenitor cells; Platelet-Derived growth factor-BB; Platelet-Derived growth factor receptor alpha
资金
- Japan Society for the Promotion of Science [16K08429, 18K06712, 16K08566, 18K06809]
- Central Research Institute of Fukuoka University [186004, 166003, 166005, 166006, 167111]
- Fukuoka University Program
- Grants-in-Aid for Scientific Research [18K06809, 18K06712, 16K08566, 16K08429] Funding Source: KAKEN
White matter lesions are associated with impairment of the blood-brain barrier (BBB), an essential component of the cerebrovasculature. The BBB allows the brain to maintain its highly specialized microenvironment by restricting entry of blood-borne substances including molecules that induce myelin damage. Accumulating evidence suggests that interactions between brain endothelial cells and neighboring cells, including oligodendrocyte progenitor cells (OPCs), are required for the induction and maintenance of BBB function. Here, we compared the ability of OPCs and oligodendrocytes to modulate BBB integrity using co-cultures of rat brain endothelial cells with OPCs or oligodendrocytes. We found that OPCs lowered the brain endothelial permeability to sodium fluorescein, and this enhancement of BBB function was prevented by treatment with AG1296 (a PDGFR alpha inhibitor). Oligodendrocytes also enhanced BBB integrity. Pharmacological inhibition of PDGFR alpha did not affect the oligodendrocyte-induced BBB facilitation. These data indicate that oligodendrocytes enhance BBB integrity through pathways other than PDGF-BB/PDGFR alpha signaling triggered by the brain endothelial cell-derived PDGF-BB. Therefore, our findings suggest that oligodendrocytes constitutively support BBB integrity through soluble factors. Crosstalk between brain endothelial cells and oligodendrocytes could play a facilitatory role in maintaining BBB integrity in the white matter.
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