EXPERIMENTAL GLIOPATHY IN THE ADULT-RAT CNS - EFFECT ON THE BLOOD-SPINAL CORD BARRIER

The expression of certain blood-brain barrier (BBB) properties in CNS endothelial cells appear to be dependent on astroglial interactions in vitro. However, evidence for direct astroglial support of BBB functio n in vivo is controversial. To determine if perivascular astroglial da mage or loss would compromise BBB function in situ, localized astrogli al degeneration was produced in adult rat spinal cords by systemic inj ections of the anti-metabolite 6-aminonicotinamide (6-AN). Between 1 a nd 5 days after 6-AN administration, microvessels in the lumbar spinal cord (blood-spinal cord barrier) were examined for the expression of several BBB markers and for leakage of endogenous and exogenous protei ns by means of immunocytochemical and histochemical procedures. Glial cells throughout the gray matter were swollen after 24 h, and by 5 day s post-injection perivascular astroglia in laminae VI-VIII appeared co mpletely degenerated. Microvessels were undamaged and continued to exp ress BBB markers such as GLUT-I, gamma-glutamyltranspeptidase, and end othelial barrier antigen in this region in a manner comparable to cont rol animals. These results suggest that differentiated, BBB-competent microvascular endothelia in situ may not depend on continuous astrogli al support to maintain these particular BBB characteristics. However, the BBB to protein appeared to be compromised; the gray matter was imm unoreactive for serum albumin and some areas were permeable to intrava scularly injected horseradish peroxidase (HRP). No increase in microva scular transport vesicles was apparent, and no open, tracer-containing interendothelial junctions were detected using standard ultrastructur al methods. Some venous structures were surrounded by hemorrhages and HRP reaction product. Thus, astrocytic injury may alter venous, and po ssibly microvascular, permeability to macromolecules. (C) 1994 Wiley-L iss, Inc.