Nitric oxide and prostaglandin E2 formation parallels blood-brain barrier disruption in an experimental rat model of bacterial meningitis

During meningitis, the host produces a plethora of signaling agents as part of a coordinated defense mechanism against invading pathogens. Nitric oxide (NO) and prostaglandin E-2 (PGE(2)) are two such inflammatory mediators produced in response to bacterial endotoxins. Disruption of the blood-brain barrier (BBB) is one of many pathophysiological consequences of meningitis. The present objective was to examine the timecourse of NO and PGE, production in relationship to BBB permeability alterations during experimentally-induced meningitis. Meningeal inflammation was elicited by intracisternal administration of the bacterial endotoxin, lipopolysaccharides (LPS; 200 mu g), and NO, PGE(2), and BBB integrity were monitored over the next 24 h. Meningeal NO production was assessed by headspace chemiluminescence; cerebrospinal fluid PGE(2) was determined by enzyme-linked immunosorbent assay (ELISA) immunoassay; and BBB integrity was determined by the brain accumulation of C-14-sucrose. Similar time-course profiles for NO and PGE(2) were observed, with a peak effect for both inflammatory mediators observed within 6-8 h after intracisternal LPS dosing. Statistically significant (p < 0.05) disruption of the BBB was observed in various brain regions. Strikingly similar temporal relationships were observed for NO and PGE(2) production and BBB disruption. These results suggest the hypothesis that NO and PGE(2) may act in conjunction to disrupt the BBB during experimental meningitis. (C) 1998 Elsevier Science Inc.