The vasculature of experimental brain tumours. Part 3. Permeability studies

The aim of this work was to elucidate the direction and time-course of transport processes which may affect the accumulation of oedema associated with experimental brain tumours. Astrocytomas were produced in BD-IX rats by intracerebral injection of cultured neoplastic glial cells. The cell line used was cloned from a culture of a primary mixed glioma induced by transplacental administration of N-ethyl-N-nitrosourea (ENU). At various times after cell injection the protein tracer horseradish peroxidase (HRP) was given to tumour-bearing rats, either intravenously or into the lateral ventricles of the brain. The movement of the HRP into tumours and surrounding brain either from blood or from ventricular cerebrospinal fluid (CSF) was studied by light and electron microscopy at various intervals after the injection of the tracer. The time-course of subsequent clearance of the HRP from the tumours and surrounding brain was also investigated. After intravenous injection, HRP rapidly penetrated all vascularized tumours and became evenly distributed within 10-20 min. The HRP remained present in sufficient quantity within the tumours to maintain this intensity for several hours, after which it gradually disappeared, showing no reaction product after 12 h. After intraventricular injection, HRP penetrated periventricular brain tissue up to a maximal distance 1-2 mm within 2 min, and the reaction product remained visible in this region for at least 20 min. In all tumour-bearing animals, HRP penetrated further into periventricular tumour tissue than into adjacent brain tissue. In large tumours HRP reaction product was seen up to 7 mm from the ventricular ependymal lining, although permeation to this distance took up to 10 min.