dinitrobenzenes and Brain-Neoplasms

The blood-brain barrier of higher vertebrates is formed by the layer of endothelial cells lining the brain microvessels. The close anatomical association between endothelial cells and perivascular astrocytic end feet suggests cooperation between these cell types in forming and maintaining the blood-brain barrier. This review considers evidence from grafting experiments, developmental studies and culture models of the brain endothelium, concerning the inductive influences acting on the endothelium, and from endothelial cells acting on perivascular astrocytes. Examples from pathology and neurotoxicology which may involve breakdown of induction are also considered.

Topics: Alzheimer Disease; Animals; Astrocytes; Blood-Brain Barrier; Brain Neoplasms; Brain Stem; Cerebrovascular Circulation; Culture Techniques; Dinitrobenzenes; Endothelium, Vascular; Nerve Tissue

Lipid-coated microbubbles (LCM) administered intravenously (i.v.) to rats bearing brain tumor, specifically enhance tumor visualization by ultrasound [1]. In order to understand the basis for this observation, we have examined the interactions of LCM with glioblastoma (C6) and gliosarcoma (9L) tumor cells in vivo and in vitro. LCM and LCM labeled with the fluorescent lipophilic dye 3,3'-dioctadecyloxacarbocyanine perchlorate (diO) were administered to rats bearing brain tumor. LCM and diO-labeled LCM were found principally at the tumor site with no evidence of label in the surrounding normal brain tissue. Analysis of the tumor by confocal laser scanning microscopy revealed that labeled LCM were inside the tumor cells. Similar analysis of LCM interactions with C6 and 9L cells in culture showed that LCM first adsorb at the surface of the cells, and with time became localized inside the cells. Binding and internalization proceeded faster at 37 degrees C than at room temperature (RT). Staining of live cells with N-(3-((2,4-dinitrophenyl)amino)propyl)-N-(3-aminopropyl) methylamine dihydrochloride (DAMP), a dye that recognizes acidic compartments, showed that the majority of internalized LCM was associated with compartments containing DAMP. If the same uptake mechanism were operative in vivo, it would indicate that a portion of LCM bypasses the reticuloendothelial system and become endocytosed directly by tumor cells.

Topics: Animals; Brain Neoplasms; Carbocyanines; Craniotomy; Dinitrobenzenes; Endocytosis; Fluorescent Dyes; Glioma; Gliosarcoma; Liposomes; Microscopy, Confocal; Microscopy, Fluorescence; Microspheres; Neoplasm Transplantation; Organelles; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Staining and Labeling; Tumor Cells, Cultured