# PATHOGENESIS AND PATHOPHYSIOLOGY OF BACTERIAL MENINGITIS

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 1991 · $197,924

## Abstract

The overall goal of the proposed research is imporvement in the
prevention, therapy, and prognosis of bacterial meningitis. This
condition remains a relatively common disease worldwide. Despite the
introduction of newer antimicrobial agents and diagnostic techniques, the
morbidity and mortality of bacterial meningitis remain unacceptably high.
The two specific aims of this proposal are discrete, initimately related,
and examine the alterations in blood-brain barrier (BBB) integrity
induced by subarachnoid space (SAS) inflammation.

The influence of bacterial meningitis on BBB permeability (BBBP) is
poorly understood. We will determine the influence of surface
characteristics (e.g. capsule, lipopolysaccharide [LPS]. fimbriae) of
meningeal pathogens (e.g. E. coli, H, influenzae) and host factors (e.g.
leukocytes, interleukin-1, tumor necrosis factor) on the traversal of
1125 I-albumin across the BBB in vivo and in vitro. The traversal of
125I- necrosis factor) on the traversal of 125I-albumin across the BBB in
vivo and vitro. The traversal of 125I- albumin (normally excluded by the
BBB) into the CSF in vivo during experimental meningitis and across an
intact physiologically "tight" monolayer o cerebral capillary endothelial
cells in tissue culture will be studied in parallel after exposure to the
following substances: selected strains of H. influenzae type b (Hib) and
E. coli to determine the role of capsul (e.g. Hib Rd-b+/02 vs Rd-/b/02;
E. coli 018:K1:H7/9 vs 018:K5H7/11),LPS (Hib COL10vsCOL10p.v. vs
COL10s.v.: E.coli 018:K1:H7/9 vs 01K1:H7/9and fimbriae (E.coli HB101 vs
HB101 (pANN801-4)vsHB101(pANN801-13/TN5-32)respectively, purified Hib
polyribosyl ribitol phosphate capsule, purified Hib LPS (classified vs
D42,01,02, COL10, col10 p.v., COL10 s.v.). Hib outer membrane vesicles,
human recombinant interleukin-I (riL-1beta), and human recombinant tumor
necrosis factor (r-TNF-alpha) alone or in combination. These studies are
symmetrical and complementaruy and reflect the influence of bacterial
meningitis (and SAS inflammation) on precise, sensitive aspects of BBB
function, critical to central nervous system (CNS) homeostatic
mechanisms.

The propensity for CNS invasion by specific micoorganisms is incompletely
defined. We will determine the adhesion of selected strains (identical to
those in specific aim 1) of H. influenzae and E. coli to rat cerebral
capillary endothelial cells and chorid plexus epithelium in tissue
culture in vitro under strictly standardized conditions. We will examine
the influence of capsular polysaccharide, LPS, and fimbriae on adhesion
to cerebral capillary endothelium and choroid plexus epithelium, the two
major sites of the BBB. These studies on the affinity of bacteria for the
components of the BBB are symmetrical and complementary to each other and
the first specific aim, and are relevant to the initiation of meningitis
and the neurotropism of meningeal pathogens. These two specific aims are
closely related and examine m...

## Key facts

- **NIH application ID:** 3127535
- **Project number:** 5R01AI017904-06
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **SAM.gov UEI:** JJG6HU8PA4S5
- **Principal Investigator:** WILLIAM M SCHELD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $197,924
- **Award type:** 5
- **Project period:** 1985-09-30 → 1993-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127535

## Citation

> US National Institutes of Health, RePORTER application 3127535, PATHOGENESIS AND PATHOPHYSIOLOGY OF BACTERIAL MENINGITIS (5R01AI017904-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127535. Licensed CC0.

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