EFFECT OF ASTROGLIAL DEGENERATION ON THE BLOOD-BRAIN-BARRIER TO PROTEIN IN NEONATAL RATS

Recent in vitro studies have suggested that astrocytes may be responsi ble for the induction of several blood-brain barrier (BBB) characteris tics. To examine this hypothesis in an in vivo situation, we have inve stigated the effect of chronic astrocytic deprivation on the BBB to pr oteins in neonatal rats. Intraperitoneal injections of the gliotoxin 6 -aminonicotinamide (6-AN) resulted in cytotoxic edema with subsequent necrobiosis of differentiated astrocytes and oligodendrocytes througho ut the CNS. Animals were sacrificed 1-5 days after chronic exposure to 6-AN during the first postnatal week. Animals sacrificed 24 h after t he final injection of 6-AN had the greatest depletion of perivascular astroglia. The BBB to exogenous protein, examined by intravascular adm inistration of horseradish peroxidase, remained intact, as did the BBB to endogenous protein as determined by immunocytochemical detection o f rat serum albumin. In no case was any leakage of protein found other than in areas that do not normally possess BBB characteristics. These data show that CNS endothelial cells retain BBB characteristics witho ut a full complement of astrocytic contacts. Since the astroglial cyto plasm was destroyed and only membrane fragments remained, we suggest t hat factors continuously produced by astroglia cannot be responsible f or the induction and maintenance of the BBB to protein, but that subst ances produced during the prenatal period may be the primary determina nt of endothelial phenotype.