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 function in vivo is controversial. To determine if perivascular astroglial damage or loss would compromise BBB function in situ, localized astroglial degeneration was produced in adult rat spinal cords by systemic injections of the anti-metabolite 6-aminonicotinamide (6-AN). Between 1 and 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 proteins by means of immunocytochemical and histochemical procedures. Glial cells throughout the gray matter were swollen after 24 h, and by 5 days post-injection perivascular astroglia in laminae VI-VIII appeared completely degenerated. Microvessels were undamaged and continued to express BBB markers such as GLUT-I, gamma-glutamyltranspeptidase, and endothelial barrier antigen in this region in a manner comparable to control animals. These results suggest that differentiated, BBB-competent microvascular endothelia in situ may not depend on continuous astroglial support to maintain these particular BBB characteristics. However, the BBB to protein appeared to be compromised; the gray matter was immunoreactive for serum albumin and some areas were permeable to intravascularly injected horseradish peroxidase (HRP). No increase in microvascular transport vesicles was apparent, and no open, tracer-containing interendothelial junctions were detected using standard ultrastructural methods. Some venous structures were surrounded by hemorrhages and HRP reaction product. Thus, astrocytic injury may alter venous, and possibly microvascular, permeability to macromolecules.
Department of Anatomy, George Washington University Medical Center, Washington, D.C. 20037.
J M
JM
Krum
D015120:6-Aminonicotinamide / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers; D001812:Blood-Brain Barrier / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006735:Horseradish Peroxidase; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009457:Neuroglia / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D009418:S100 Proteins / Q000096:biosynthesis; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D009418:S100 Proteins; D015120:6-Aminonicotinamide; D006735:Horseradish Peroxidase; D005723:gamma-Glutamyltransferase