121 INTRACISTERNALLY (ic) GIVEN E.COLI O 111 B 4 ENDOTOXIN (LPS) OPENS THE BLOOD-BRAIN BARRIER (BBB) FOR NA-FLUORESCEIN (NaF) IN NEW BORN PIGLETS

Abstract

Despite decades of investigating the BBB, there remains a distinct paucity of data regarding its response to infections. We have studied the pial-arachnoid microvasculature in vivo in newborn piglets through an open cranial window using fluorescence photomacroscope giving 20 μg (n=6) -Group 1- and 200 μg (n=6) -Group 2- LPS ic. Control animals (n=6) -Group 3- were given mock cerebrospinal fluid (CSF). CSF LPS concentration was determined using chromogenic limulus amcbocyte lysate assay. NaF (MW=376) given intravenously was used as a BBB permeability marker and brain NaF uptake (BNU) was measured by a spectrofluorometer. In Group 3 (the BBB remained light through the experimental period (4 hours), there were neither fluorescein extravasation nor significant BNU. In Group 1 the BBB was opened (extensive fluorescein leakage) 70.5±10.5 min after the ic LPS injection, and CSF LPS levels was significantly elevated (0.70±0.10 EU/ml) at that time compared to the value measured at the start of the experiment (0.14±0.04 EU/ml; p<0.05). There was an elevation in BNU (3.0±0.7 μg NaFxmg−1 protein/μg NaFxμl−1 serum) at the time of sacrifice (4 hours). In Group 2 the BBB was opened significantly earlier (55.2±4.1 min), and CSF LPS content (1.18±0.10 EU/ml) and BNU (5.9±0.9 μg NaFxmg−1 protein/μg NaFxμl−1 serum) were also highly elevated compared to the Group 1 (p<0.05 in each parameter). It is concluded that ic given LPS, as a model of neonatal purulent meningitis, results in a dose dependent opening of the BBB for NaF, and in marked changes in the extracellular fluid space of the brain. (All values are mean±SD.)