# PATHOGENESIS OF NEONATAL NECROTIZING ENTEROCOLITIS

> **NIH NIH K08** · EVANSTON HOSPITAL · 1994 · $74,520

## Abstract

The emphasis of this proposal is to characterize a neonatal animal model
of necroitizing enterocolitis (NEC) and to investigate the pathogenesis
of this devastating disease of premature infants as it relates to PAF and
other inflammatory mediators.  Although intestinal injury in adult
animals has been shown to be predominantly mediated by PAF, the etiology
of neonatal NEC may be significantly different from adult bowel necrosis,
and the importance of PAF in NEC in unknown.  Neonatal NEC will be
reproduced in newborn rats to simulate the human condition by exposing
the animals to the known risk factors of NEC, i.e. formula feeding,
hypoxia, and bacterial colonization.  Subsequently, the roles of PAF and
other mediators (endotoxin, endothelin, tumor necrosis factor, and
thromboxane) will be evaluated in this model by 1) measuring plasma (all)
and intestinal PAF, 2) studying PAF regulating enzyme expression and
activity (using enzyme assays, Norther blot analysis, and in situ
hybridization), 3) studying PAF receptor binding regulation and receptor
gene transcription, and 4) inhibition of PAF and other mediators using
specific inhibitors and monoclonal antibodies.  In addition, endothelial
cell monolayers will be used to evaluate interactions at the cellular
level between hypoxia, PAF, and endothelin.  Finally, premature human
neonates will be studied to test the hypothesis that feeding stimulates
endotoxin release, phospholipase A2 activation, PAF synthesis, and NEC.
Results from these studies may suggest new therapeutic strategies for the
prevention and treatment of neonatal NEC.

The candidate is an academic neonatologist trained in the biochemical
evaluation of PAF as it relates to neonatal pathophysiology.  Application
for the Clinical Investigator Award is designed to support protected time
away from clinical concerns in order to solidify training in molecular
biological techniques including Northern blot analysis and in situ
hybridization.  With the acquisition of these skills, this researcher
will become competitive independently for extramural funding.

Molecular biology training will be provided by the sponsor who is an
established investigator; this training will take place at Children's
Memorial Hospital where the sponsor maintains her laboratory.  This award
will enable the candidate to develop and skills necessary to accomplish
these pursuits in my laboratory at Evanston Hospital.

## Key facts

- **NIH application ID:** 2194507
- **Project number:** 5K08HD000999-02
- **Recipient organization:** EVANSTON HOSPITAL
- **Principal Investigator:** MICHAEL S CAPLAN
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $74,520
- **Award type:** 5
- **Project period:** 1993-01-01 → 1997-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194507

## Citation

> US National Institutes of Health, RePORTER application 2194507, PATHOGENESIS OF NEONATAL NECROTIZING ENTEROCOLITIS (5K08HD000999-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194507. Licensed CC0.

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