Intracarotid tumor necrosis factor-alpha administration increases the blood-brain barrier permeability in cerebral cortex of the newborn pig: quantitative aspects of double-labelling studies and confocal laser scanning analysis.
Tumor necrosis factor-alpha (TNF-alpha) plays a crucial role in the pathogenesis of the central nervous system infections. The aim of the present study was to analyze quantitatively the changes in the blood-brain barrier (BBB) permeability after the intracarotid injection of TNF-alpha. Recombinant human TNF-alpha was injected into the left internal carotid artery of anesthetized newborn pigs (n = 48) in the doses of 0, 1000, 10 000 and 100 000 IU, respectively. Before, as well as 1, 2, 4, 8, and 16 h after the challenge, the extravasation of a small (sodium fluorescein (SF), mw 376), and a large (Evan's blue-albumin (EBA), mw 67 000) tracer was determined concomitantly by spectrophotometry in the cerebral cortex of the animals. There was a time- and dose-dependent increase in BBB permeability both for SF and EBA; however, significant (P < 0.05) BBB opening for albumin only developed 2 h after the challenge. In the morphological study the same excitable tracers, identical experimental protocol and groups were used. Cryostat sections of brain tissue were viewed for optical sectioning with a confocal laser scanning microscope equipped with an argon/krypton ion laser. A diffuse BBB opening for SF and a moderate perivascular extravasation for EBA were found in the cortices of TNF-alpha-treated animals. We conclude that significant increases in intravascular TNF-alpha-concentration during neonatal infections may result in vasogenic brain edema formation.
Abraham
C S
CS
Department of Pediatrics, Albert Szent-Gyorgyi Medical University, Szeged, Hungary. abraham@pedia.szote.u-szeged.hu
Deli
M A
MA
Joo
F
F
Megyeri
P
P
Torpier
G
G
D000418:Albumins / Q000493:pharmacokinetics*; D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002339:Carotid Arteries; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000378:metabolism / Q000503:physiopathology; D005070:Evans Blue / Q000493:pharmacokinetics*; D005260:Female; D019793:Fluorescein; D005452:Fluoresceins / Q000493:pharmacokinetics*; D007269:Injections, Intra-Arterial; D007834:Lasers; D008297:Male; D018613:Microscopy, Confocal; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000418:Albumins; D005452:Fluoresceins; D014409:Tumor Necrosis Factor-alpha; D005070:Evans Blue; D019793:Fluorescein