DISTURBED BRAIN PURINE METABOLISM RESULTS IN A GROSS OPENING OF THE BLOOD-BRAIN-BARRIER IN NEWBORN PIGLETS FOLLOWING EXPERIMENTAL PNEUMOTHORAX

Changes in the permeability of pial-arachnoideal microvessels [30-210 μm), of the blood-brain barrier (BBB), were intravitally studied by fluorescent microscopy and compared to the hypoxanthine (HX) level of cerebrospinal fluid (CSF) in newborn piglets (n = 24) using the open cranial window technique. Eight animals served as controls (Group 1), the others were studied in the course of bilateral experimental pneumothorax (BEP) using low (Na+-fluorescein, MW 376, Group 2) and large molecular weight (FITC dextran, MW 40 000, Group 3) fluorescent tracer molecules. Cisternal CSF was sampled from the animals: 8 piglets from Group 1, and 4-4 piglets from Groups 2 and 3 at different stages of pathological condition: (i) at the critical (C) stage (severe acidosis, bradycardia, arterial hypotension and hypoxaemia) and also (ii) at the recovery (R) stage (mild metabolic acidosis, tachycardia, arterial hypotension) and the HX concentration was determined with high-pressure liquid chromatography. In Group 1 neither low (n = 4) nor large (n = 4) molecular weight tracers penetrated BBB. In Group 2, however, the fluorescein dye passed BBB as a spotty leakage in animals at C stage (n = 8). Diffuse fluorescein penetration was seen at R stage, too (n = 4). In Group 3 no change in permeability was found at C stages (n = 8), but at R stage (n = 4), 2h after the primary hypoxic insult, when the animals had recovered from cardiovascular and metabolic shock, the tracer passed locally the microvascular wall and appeared as leaky spots (number of leaky sites = 2.3 ± 0.4 0.10 cm2, X ̄ ± SE. The HX content in the CSF was significantly elevated (P < 0.05) at stage C (26.39 ± 3.2 μM/l, X ̄, ± SE, compared to data measured in Group 1 (8.4 ± 1.7 μM/l, X ̄ ± SE. At stage R, it proved to be significantly lower (P < 0.05) than in stage C, but still remained elevated (17.7 ± 2.1 μM/l, X ̄ ± SE; P < 0.05 vs. Group 1). Our results draw the attention of the size-dependent gross opening of the BBB in different stages of BEP and to the possible importance in the pathogenesis of mediators deriving from the disturbed brain purine metabolism. © 1990.