Blood-brain barrier changes following intracerebral injection of human recombinant tumor necrosis factor-alpha in the rat.
Human recombinant tumor necrosis factor-alpha (rTNF-alpha) was administered to normal Fischer 344 rats by stereotaxic intracerebral (IC) injection. Animals receiving a single injection of either 6 x 10(4) U rTNF-alpha or an equivalent volume of excipient (vehicle) in their right parietal lobe. In order to demonstrate any effects rTNF-alpha might have on the blood-brain barrier (BBB), two studies were conducted, one employing exogenous horseradish peroxidase (HRP,44 kD) as a tracer of BBB permeability and the other using endogenous IgG (150 kD). Rats given rTNF-alpha showed transitory BBB permeability to HRP by 24 hours post-injection; this BBB compromise was determined to be no longer than 60 hours. In the other study, IgG was seen to cross the BBB by 48 hours post-rTNF-alpha injection. Alternatively, rats injected IC with excipient showed only limited BBB opening as a result of injection-induced trauma. We conclude that human rTNF-alpha, injected IC into normal rats triggers a temporary breakdown in BBB integrity which begins sometimes between 12 and 24 hours post-injection, is large enough to permit macromolecules of at least 150 kD to pass, and resolves by 72 hours post-injection.
Wright
J L
JL
Department of Anatomy, Virginia Commonwealth University, Medical College of Virginia, Richmond.
Merchant
R E
RE
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D005260:Female; D006735:Horseradish Peroxidase / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology
D007074:Immunoglobulin G; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D006735:Horseradish Peroxidase