INTRACISTERNALLY GIVEN ELASTASE/E/ENHANCES BLOOD-BRAIN BARRIER/BBB/ PERMEABILITY IN NEWBORN PIGLETS

Abstract

Elastase, released during polymorphonuclear phagocytosis, is a potentially tissue damaging enzyme. We investigated its effect on BBB-permeability in newborn piglets. 11 anesthetized animals /Group 1/ were given 1 μg porcine E in 0,5 ml artificial CSF intracisternally, 7 piglets (given mock CSE) served as controls /Group 2. Through 4 hours afler E administration permeability changes of pial microvessels were followed intravitally by fluorescence photomacroscope using an open cranial window. Tracer was 1 % Na-fluorescein (NaF). Physiological parameters (HR, MABP, blood gases, acid-base status) were continuously monitored. Spolly NaF extravasation was seen in all animals in Group 1 (meantime elapsed from E administration: 78±13 min.), but the BBB remained tight in Group 2 till the end of the experiments, α1-proteinase inhibitor /α1-VI/ activity was measured in sera and in CSF at 0, 2, 4 h after E injection. In CSF of Group 1 it increased significantly (Oh: 8,9±4,1 - 2h: 173,7 ± 46,5 - 4h 416,8±132,9 μg/ml), while its activity wasn't elevated in Group 2 (Oth: 8,8 ± 4,6 2h: 12,8 ± 3,9 - 4h 6,7±2,4 μg/m]). In the sera measured paralelly, α1-PI activity remained constant in both groups. Free E wasn't detectable in all samples. White blood cell count elevated in CSF (Oh: 1 ± 1 - 4h: 63±14 μl−1) and in sera (Oh: 2453 ± 355 - 4h: 7518 ± 751 μl−1) in Group 1, but didn't change in Group 2. We conclude ihat elastase may play an additional role in BBB injury during neonatal meningitis. All values are: x, + S.E.