Potential role of nitric oxide in the pathophysiology of experimental bacterial meningitis in rats

Abstract

We have investigated the possible role of nitric oxide (NO) in the pathophysiology of bacterial meningitis (BM) by using the rat model of experimental BM. The nitrite concentration in cerebrospinal fluid (CSF) was used as a measure of NO production in vivo since NO rapidly degrades to nitrite and nitrate. Rats were inoculated intracisternally with live bacteria (5 ؋ 10 6 CFU of Haemophilus influenzae type b strain DL42 or Rd ؊ /b ؉ /O2), with bacterial endotoxin (20 ng of DL42 lipooligosaccharide [LOS] or 200 ng of Escherichia coli lipopolysaccharide), or with a saline control vehicle. CSF samples were collected preinoculation and at the time of maximal alteration in blood-brain barrier permeability (BBBP). CSF [nitrite] was quantified by measuring A 550 after addition of the Greiss reagent and comparison to a standard curve of sodium nitrite. Rats inoculated with either DL42, Rd ؊ /b ؉ /O2, LOS, or lipopolysaccharide demonstrated a significantly elevated mean peak CSF [nitrite] (8.34, 15.62, 10.75, and 10.44 mM, respectively) versus the concentration prior to treatment and/or those in saline-treated animals (5.29 and 5.33 mM, respectively; P < 0.05 for each comparison). We then determined if there was a correlation between CSF [nitrite] and percent BBBP (%BBBP) at various time points postinoculation with Rd ؊ /b ؉ /O2. %BBBP was defined as the concentration of systemically administered 125

Blood-brain barrier disruption highly induces aquaporin-4 mRNA and protein in perivascular and parenchymal astrocytes: Protective effect by estradiol treatment in ovariectomized animals

“…Consequently, it is difficult to draw a conclusion about the response of the injured brain exposed to brain edema. To shed light on this issue, we used the intraparenchymal injection of LPS as a specific model for BBB disruption (Arditi et al, 1993; Boje, 1995; Buster et al, 1995; de Vries et al, 1996). The time‐course analysis revealed that the first signs of BBB disruption were already evident 6 hr post‐lesion, which coincided with maximal induction of AQP4 in perivascular glial processes, thus suggesting that disruption of the BBB is a very efficient inducer of AQP4 expression in these cells.…”

Meningitis-Associated Central Nervous System Complications are Mediated by the Activation of Poly(ADP-ribose) Polymerase

“…The major CNS complications causing brain injury comprise cerebrovascular alterations, brain edema, hydrocephalus, and increased intracranial pressure (ICP). Although there is substantial evidence that ROS and RNI are central mediators of meningitisassociated CNS complications (Koedel et al, 1995;Buster et al, 1995;Leib et al, 1996;Kastenbauer et al, 1999), the mechanisms underlying ROS-and RNIinduced brain injury in meningitis are poorly defined.…”

Neisseria meningitidis‐induced death of cerebrovascular endothelium: mechanisms triggering transcriptional activation of inducible nitric oxide synthase

“…This NOS-2 response in the host, while antimicrobial (Fang 1997;Leib et al 1998), may also contribute to the ensuing pathophysiology (Tunkel and Scheld 1993;Shenep and Tuomanen 1998). Levels of NO correlate with alterations in BBB properties (Buster et al 1995;Mayhan 2000) and the severity of meningitis (Deng et al 2001), and also changes in BBB permeability (Buster et al 1995), is reversed by NOS inhibition. Recently, there have been reports of increased expression of both NOS-2 and NOS-3 in rodents experimentally infected with Streptococcus pneumoniae, correlating with rat blood-labyrinth ) and mouse BBB disruption (Winkler et al 2001).…”

“…1998), may also contribute to the ensuing pathophysiology (Tunkel and Scheld 1993; Shenep and Tuomanen 1998). Levels of NO correlate with alterations in BBB properties (Buster et al . 1995; Mayhan 2000) and the severity of meningitis (Deng et al .…”