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

Brain vasculature forms the bloodbrain 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.