VEGF-dependent continuous angiogenesis in the median eminence of adult mice.

Brain vasculature forms the blood-brain barrier (BBB) that restricts the movement of molecules between the brain and blood, but the capillary of the median eminence (ME) lacks the BBB for secretion of adenohypophysial hormone-releasing peptides. In the present study, we aimed to elucidate whether continuous angiogenesis occurs in the ME of adult mice. By using a mitotic marker, bromodeoxyuridine (BrdU), we demonstrated that new endothelial cells were born continuously in the ME of adults. Prominent expression of NG2, platelet-derived growth factor receptor B (PDGFRB), and delta-like ligand 4 was observed at pericytes of adults, although the expression of these angiogenesis-associated proteins has been shown to be at low or trace levels in adult mature capillary. In addition, vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, was expressed highly in the nervous parenchyma of the ME. Expression of VEGF receptor 2 (VEGFR2) was observed at endothelial cells in the external zone and at somatodendrites in the internal zone. Finally, a VEGFR- and PDGFR-associated tyrosine kinase inhibitor, SU11248, significantly decreased the number of BrdU-positive proliferating endothelial cells and parenchyma cells. In conclusion, the present study demonstrates VEGF-dependent continuous angiogenesis in the ME of adult mouse brains under normal conditions, which provides new insight into our understanding of neurosecretion in the ME.