Tumoral micro-blood vessels and vascular microenvironment in human astrocytic tumors. A transmission electron microscopy study

Abstract

The development of peritumoral edema is thought to be due to extravasation of plasma water and macromolecules through a defective blood-brain barrier (BBB), but the exact mechanism by which occurs is poorly understood. The aim of this study was analyze at submicroscopic level the morphological changes in both micro-blood vessels and vascular microenvironment of astrocytic tumors in an attempt of understanding the pathological aspects that may help in the future researches for the design of future therapeutic strategies. Biopsies of 25 patients with pathological diagnosis of astrocytic tumors were examined with the transmission electron microscope. Both open and close tight junctions were observed in the micro-blood vessels, inclusive in a same tumor. Cytoskeletal disorganization associated with disintegrated perijunctional actin filaments were seen. The paracellular space showed enlargement and commonly occupied by fluid proteinaceous, endothelial cells display oncotic and ischemic changes, basal lamina reveals enlargement, edema, vacuolization and collagen fibers disposed in irregular array. Pericytes exhibited edema and phagocytoced material, astrocytic perivascular-feet showed signs of oncosis and necrosis, co-option vessels totally surrounding by neoplastic cells also were seen. The ultrastructural abnormalities observed in both junctional complexes and vascular microenvironment suggest a multi-factorial pathobiology process, probably hypoxia intratumoral, calcium overload in endothelial cells, and degradative effects of metalloproteinases over the basal membrane appear as determinant factors that leading to structural modifications of junctional complexes, therefore, treatment with both HIF-1alpha and metalloproteinases inhibitors possibly can contribute with the pharmacological handling of the peritumoral edema associated with astrocytic tumors.