Effect of astroglial degeneration on the blood-brain barrier to protein in neonatal rats.
Recent in vitro studies have suggested that astrocytes may be responsible for the induction of several blood-brain barrier (BBB) characteristics. To examine this hypothesis in an in vivo situation, we have investigated the effect of chronic astrocytic deprivation on the BBB to proteins in neonatal rats. Intraperitoneal injections of the gliotoxin 6-aminonicotinamide (6-AN) resulted in cytotoxic edema with subsequent necrobiosis of differentiated astrocytes and oligodendrocytes throughout the CNS. Animals were sacrificed 1-5 days after chronic exposure to 6-AN during the first postnatal week. Animals sacrificed 24 h after the final injection of 6-AN had the greatest depletion of perivascular astroglia. The BBB to exogenous protein, examined by intravascular administration of horseradish peroxidase, remained intact, as did the BBB to endogenous protein as determined by immunocytochemical detection of 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 without a full complement of astrocytic contacts. Since the astroglial cytoplasm was destroyed and only membrane fragments remained, we suggest that factors continuously produced by astroglia cannot be responsible for the induction and maintenance of the BBB to protein, but that substances produced during the prenatal period may be the primary determinant of endothelial phenotype.
Krum
J M
JM
Department of Anatomy, George Washington University Medical Center, Washington, DC 20037.
Rosenstein
J M
JM
D015120:6-Aminonicotinamide; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000502:physiology*; D009410:Nerve Degeneration / Q000502:physiology*; D051381:Rats
D001798:Blood Proteins; D015120:6-Aminonicotinamide