Development of tight junction molecules in blood vessels of germinal matrix, cerebral cortex, and white matter

Abstract

Tight junction (TJ) molecules confer cell-to-cell adhesion to endothelial cells and, thus, provide structural integrity to blood vessels. Therefore, decreased expression of these molecules may be a cause of germinal matrix (GM) fragility and their propensity to hemorrhage in premature infants. The objective of this study was to compare the expression of endothelial TJ molecules, including claudin-5, occludin, and junction adhesion molecules (JAM), among blood vessels of GM, cortex, and white matter for fetuses and premature infants of gestational age 16-40 wk, and to examine their maturational changes with advancing gestational age. We measured the expression of claudin-1, claudin-5, occludin, and JAM in GM, cortex, and white matter in postmortem brain samples. We performed immunohistochemical staining on brain sections and Western blot to quantify these molecules. We found that claudin-5, occludin, and JAM-1 were expressed as early as 16 wk in GM, cortex, and white matter. Claudin-1, JAM-2, and JAM-3 were not detected in the GM, cortex, and white matter. Claudin-5, occludin, and JAM-1 did not change significantly as a function of gestational age. There was no significant difference in the expression of these molecules in the vasculature of GM compared with cortex and white matter. Because the primary endothelial TJ molecules, including claudin-5, occludin, and JAM-1, are expressed as early as 16 wk in the blood brain barrier and since as they are not decreased in GM vasculature compared with cortex and white matter, they are unlikely to be responsible for GM fragility and vulnerability to hemorrhage in premature infants.