The dynamics of blood-brain barrier breakdown in an experimental model of glial cell degeneration

This study was undertaken to investigate the dynamics of blood-brain barrie r breakdown in an lit vivo rat model of selective CNS vulnerability. 1,3-Di nitrobenzene was used to induce rapid glial degeneration in highly defined areas of the brainstem. Leakage of fluorescent dextran was used to demonstr ate the breakdown of the blood-brain barrier, and antibodies to glial and n euronal specific proteins to assess the accompanying cell changes. Beginnin g 18 h after a toxic dose of dinitrobenzene and before loss of glial enshea thment, a sub-population of blood vessels became permeable to fluorescent d extrans below 500,000 mol, wt in size. By 24 h most macroglial cells had be en lost from within susceptible areas and vascular leakage had reached peak levels. Macrophage invasion was detected three days following dinitrobenze ne. Vessels continued to leak up to four days after the lesion was formed, but by six days blood-brain barrier integrity was largely re-established. M ultiple tracer injections over time demonstrated that a single sub-populati on of vessels was leaking during the experimental period. From these findings we conclude that blood-brain barrier breakdown in this model system is highly selective, graded in extent and molecular weight spe cificity and not a direct consequence of astrocyte degeneration or microgli al activation. This system could be useful in modeling human CNS pathologic al processes with a vascular component and for understanding in vivo glial blood-brain barrier interactions. Crown Copyright (C) 2001 Published by Els evier Science Ltd on behalf of IBRO. All rights reserved.