# PATHOGENESIS AND PATHOPHYSIOLOGY OF BACTERIAL MENINGITIS

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 1987 · $141,706

## Abstract

Bacterial meningitis is still a common disease worldwide.  Despite the
introduction of antibiotics, the morbidity and mortality rates have not
improved in more than 30 years.  We will examine two specific aspects of
the pathogenesis and pathophysiology of bacterial meningitis by in vitro
and experimental rat meningitis in vivo techniques in an attempt to improve
the results of treatment and prevention.  Both areas of investigation are
discrete and intimately related to the interaction of meningeal pathogens
and the blood-brain barrier (BBB).

The precise effect(s) of meningitis on the morphology and transport
characteristics of the BBB are unknown.  We will quantitate the morphologic
alterations of isolated rat cerebral capillaries (a major site of the BBB)
induced after incubation with meningeal pathogens (E. coli, H influenzae,
S. pneumoniae, S. agalactiae) in vitro.  We will determine the influence of
E. coli and H. influenzae capsule and lipopolysaccharide (LPS) on the
morphology of cerebral capillaries in vitro and correlate these results
with changes in BBB permeability in rats with experimental meningitis by
quantitative autoradiography.  We will examine the effect of E. coli
icubation on the transport of glucose and penicillin across the BBB in
isolated cerebral microvessles and cannulated single cerebral arterioles in
vitro.

The route of invasion of the cerebrospinal fluid (CSF), and the reasons for
neutropism of only a small group of bacterial species during bacteremia are
unknown.  We will examine bacterial affinity fo the central nervous system
by studing adhesion of E. coli and H. influenzae to a major site of the
BBB, infant and adult rat cerebral capillary endothelial cells in tissue
culture.  The E. coli and H. influenzae strains examined for adhesion to
the endothelial cells will be identical to those used to study the
influence of meningitis in BBB morphology and transport properties above.
These strains wil be chosen from clinical isolates, mutants, and laboratory
DNA tansformants of well-characterized phenotype to precisely define the
role of encapsulation, amount of capsular polyribosephoshate expressed, and
cell-surface lipopolysaccharide on adhesion to, and alterations produced
in, the BBB.

## Key facts

- **NIH application ID:** 3127533
- **Project number:** 5R01AI017904-03
- **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:** 1987
- **Award amount:** $141,706
- **Award type:** 5
- **Project period:** 1985-09-30 → 1988-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127533

## Citation

> US National Institutes of Health, RePORTER application 3127533, PATHOGENESIS AND PATHOPHYSIOLOGY OF BACTERIAL MENINGITIS (5R01AI017904-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127533. Licensed CC0.

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