Angiogenesis in developing rat brain: An in vivo and in vitro study

Abstract

Key words: angiogenesis --cultured endothelial cells --[3H]thymidine autoradiography -endothelial cell growth factor --rat brain development Brain capillary proliferation in postnatal rats was measured in vivo by [3H]thymidine autoradiography. Maximal capillary proliferation occurred between 5 and 9 postnatal days, and was 40 times greater than in the adult. To test the hypothesis that soluble angiogenesis factors play a role in this developmental vascularization of brain, we prepared extracts from the brains of 6-day-old rats at the peak of proliferative activity, and from adults when it was lowest. We assayed them using an in vitro growth system measuring [3H]thymidine incorporation into cultured brain capillary endothelial cells. Extracts prepared from either 6-day or adult rats and containing 150/~g/ml protein caused more than a 4-fold stimulation of the endothelial cells, increasing to 8-fold at a concentration of 150011g/ml. The presence of growth-promoting activity in brain extracts from both adult and immature rats suggests that soluble angiogenesis factors may be present in the brain throughout life, but are unavailable for stimulation of in vivo capillary growth unless released or activated by an appropriate stimulus.

Bone Marrow-Derived Endothelial Progenitor Cells Participate in Cerebral Neovascularization After Focal Cerebral Ischemia in the Adult Mouse

“…This is consistent with previous reports that functional imaging of stroke patients shows increased cerebral blood flow and metabolism in tissue surrounding focal brain infarcts. 21 Our observation of a near absence of BrdU immunoreactive cells in vessels of the contralateral hemisphere is consistent with that proliferation of the cerebral endothelial cells ceases, 8,9 whereas increases in proliferated endothelial cells in the ischemic vessels may reflect angiogenesis. Formation of new vessels may arise from the proliferation and migration of endothelial cells from the adjacent tissue and from circulating endothelial progenitor cells.…”

“…5,6 In the adult brain, proliferation of the cerebral endothelial cells ceases, and the turnover rate of endothelial cells is approximately 3 years. 8,9 Studies from human and experimental stroke indicate that neovascularization is present in the adult brain after ischemia. 10,11 However, development of new blood vessels in ischemic adult brain is incompletely understood, and it remains unknown whether newly formed vessels are induced by proliferation of preexisting vascular endothelial cells or by recruitment of circulating endothelial progenitor cells to the brain after stroke.…”

Erythropoietin Promotes Neuronal Replacement Through Revascularization and Neurogenesis After Neonatal Hypoxia/Ischemia in Rats

“…22 Consistent with this, we found that BrdU uptake in progenitor cells associated with functional vessels was increased in control animals within the first 3 days assayed corresponding with postnatal days 7 to 9 ( Figure 1F). …”

“…22 In our study, during the period of new vessel accumulation, a limited number of newly formed neuronal progenitors migrated away from the SVZ to the ST and CTX in naïve animals ( Figure 4). After H/I, functional revascularization in the ischemic boundary was severely suppressed over the first week and never completely restored compared with age-matched naïve animals ( Figure 1).…”

Heme Regulation in Traumatic Brain Injury: Relevance to the Adult and Developing Brain

“…The formation of synapses, myelination, dendritic growth, and vascular proliferation are all crucial aspects of normal maturation of the brain (Dobbing and Sands, 1979;McDonald and Johnston, 1990;Paxinos, 1995;Robertson et al, 1985). How HO interacts with these developmental events is not entirely clear.…”