Intracarotid tumor necrosis factor-α 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

• Published in: Neuroscience letters 1996-04, Vol.208 (2), p.85-88
• Main Authors: Ábrahám, Csongor S., Deli, Mária A., Joó, Ferenc, Megyeri, Pál, Torpier, Gérard
• Format: Article
• Language: English
• Subjects: Albumins - pharmacokinetics; Animals; Animals, Newborn; Biological and medical sciences; Blood-brain barrier; Blood-Brain Barrier - drug effects; Brain edema; Carotid Arteries; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cerebral Cortex - blood supply; Cerebral Cortex - metabolism; Cerebral Cortex - physiopathology; Dose-Response Relationship, Drug; Edema - metabolism; Edema - physiopathology; Evans Blue - pharmacokinetics; Female; Fluorescein; Fluoresceins - pharmacokinetics; Fundamental and applied biological sciences. Psychology; Injections, Intra-Arterial; Lasers; Male; Microscopy, Confocal; Swine; Time Factors; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-α; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/0304-3940(96)12546-5

Tumor necrosis factor-α (TNF-α) 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-α. Recombinant human TNF-α 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-α-treated animals. We conclude that significant increases in intravascular TNF-α-concentration during neonatal infections may result in vasogenic brain edema formation.