Neuronal VEGF expression correlates with angiogenesis in postnatal developing rat brain

When exposed to chronic sublethal hypoxia the developing brain responds wit h increases in permeability and angiogenesis. Vascular endothelial growth f actor (VEGF) may mediate this response. Here, we present data on the locali zation of VEGF in the rat brain cortex during postnatal development and its correlation to vascularization. We reared newborn rats under normoxic cond itions and in hypoxic chambers (FiO(2) 9.5%), removed them at postnatal day s (P) 3, 8, 13, 24, and 33 and prepared the cortical brain tissue for immun ohistochemistry, in;situ hybridization (ISH), Western blot analyses and ves sel density counting. When compared to age-matched controls, hypoxic-reared animals displayed a significant increase in platelet endothelial cell adhe sion molecule 1 (PECAM-1) protein levels, cerebral microvascular lumen diam eter and number and density of vessels (number of capillaries per area). In control animals, ISH and immunohistochemistry revealed that localization o f VEGF is restricted almost exclusively to cortical neurons at early stages of development. As the vascular bed begins to stabilize, predominant VEGF expression switches to maturing glial cells which invest vessels while neur onal expression is reduced to a basal level. In hypoxic animals, early loca lization of VEGF is also restricted to cortical neurons, however, during la ter developmental stages, glial cells express elevated levels of VEGF prote in and high neuronal expression also persists. Thus chronic sublethal hypox ia disrupts the temporal-spatial expression of VEGF, which correlates with continuing hypoxia-driven angiogenesis. (C) 2000 Elsevier Science B.V. All rights reserved.