INTRACAROTID TUMOR-NECROSIS-FACTOR-ALPHA ADMINISTRATION INCREASES THEBLOOD-BRAIN-BARRIER PERMEABILITY IN CEREBRAL-CORTEX OF THE NEWBORN PIG - QUANTITATIVE ASPECTS OF DOUBLE-LABELING STUDIES AND CONFOCAL LASER-SCANNING ANALYSIS

Tumor necrosis factor-alpha (TNF-alpha) plays a crucial role in the pa thogenesis of the central nervous system infections. The aim of the pr esent study was to analyze quantitatively the changes in the blood-bra in 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 (sod ium fluorescein (SF), mw 376), and a large (Evan's blue-albumin (EBA), mw 67 000) tracer was determined concomitantly by spectrophotometry i n the cerebral cortex of the animals. There was a time- and dose-depen dent increase in BBB permeability both for SF and EBA; however, signif icant (P < 0.05) BBB opening for albumin only developed 2 h after the challenge. In the morphological study the same excitable tracers, iden tical 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 diffu se BBB opening for SF and a moderate perivascular extravasation for EB A were found in the cortices of TNF-alpha-treated animals. We conclude that significant increases in intravascular TNF-alpha-concentration d uring neonatal infections may result in vasogenic brain edema formatio n.