Cerebral angiogenesis induced by growth factors: intravital microscopic studies using models

Abstract

Pharmacological induction of angiogenesis is a new treatment of cerebrovascular insufficiency without surgical treatment. It is an urgent task to investigate the dynamic process of angiogenesis and of the microvascular perfusion of the cerebral neoplastic tissue in vivo. The present study is concerned with microcirculatory aspects of cerebral neocapillaries in vivo. A novel model of cerebral angiogenesis was developed by inducing cerebral neocapillaries in mice using growth factors such as basic fibroblast growth factor (bFGF) and platelet‐derived growth factor (PDGF). By a direct observation of the neocapillary microcirculation under a fluorescence videomicroscope, the neocapillary density, diameter and red cell velocity were measured to evaluate the development and remodeling of the neocapillaries with the number of days after incubation. The neocapillary response to topically applied acetylcholine (ACh) was examined by measuring changes in the diameter and red cell velocity. It was shown that PDGF‐induced neocapillaries was dilated in response to ACh on day 28 after incubation, while bFGF‐induced neocapillaries was not. Furthermore, the neocapillary pericytes were observed using confocal laser microscopy, based on the fluorescence immunohistochemical images of the neoplastic tissue. Several pericytes, stained with anti‐NG₂, appeared in the neocapillaries. It was suggested that these pericytes might be recruited in the neocapillaries to regulate blood flow without vascular smooth muscle.