Blood-brain barrier changes following intracerebral injection of human recombinant tumor necrosis factor-α in the rat

• Published in: Journal of neuro-oncology Vol. 20; no. 1; pp. 17 - 25
• Main Authors: WRIGHT, J. L, MERCHANT, R. E
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01-01-1994
• Subjects: Animals; Biological and medical sciences; Blood-Brain Barrier - drug effects; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Female; Fundamental and applied biological sciences. Psychology; Horseradish Peroxidase - analysis; Humans; Immunoglobulin G - analysis; Rats; Rats, Inbred F344; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacology; Tumor Necrosis Factor-alpha - administration & dosage; Tumor Necrosis Factor-alpha - pharmacology; Vertebrates: nervous system and sense organs; Vertebrata; Mammalia; Histopathology; Rat; Animal; Cytokine; Rodentia; Exploration; Experimental study; Blood brain barrier; Tumor necrosis factor α
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/BF01057957

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.