# PATHOGENESIS OF PERINATAL HYPOXIC-ISCHEMIC BRAIN DAMAGE

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 1994 · $158,590

## Abstract

The overall objective of the present research is to elucidate biochemical
and physiologic mechanisms responsible for perinatal hypoxic-ischemic brain
damage and to develop methods which will arrest or retard these processes.
Specific aims include: 1) to identify and examine the evolution of the
threshold lesion which arises from cerebral hypoxia-ischemia in the
immature rat; 2) to characterize the early cerebrovascular and metabolic
events which precede or parallel the evolution of identifiable lesions
resulting from cerebral hypoxia-ischemia in the immature rat; 3) to
determine the influence of alterations in glucose and lactate homeostasis
on hypoxic-ischemic brain damage in the immature rat; and 4) to investigate
biochemical mechanisms by which specific pharmacologic interventions
(calcium channel blockers, xanthine oxidase inhibitors, excitatory
neurotransmitter receptor inhibitors) protect the perinatal brain from
hypoxic-ischemic brain damage.  To accomplish these goals, we plan to use
the following analytical techniques: 1) modification of the iodo-[14C]-
antipyrine to measure regional cerebral blood flow; 2) modification of the
2-deoxy-[14C]-glucose technique to measure regional cerebral glucose
utilization; 3) in vivo analysis of glycolytic and Krebs cycle
intermediates and high-energy phosphate reserves in brain tissue; 4)
determination of cerebral energy utilization, intracellular pH, and the
redox state of brain tissue on a global, regional and micro-regional basis;
5) regional analysis of calcium uptake and turnover by brain using [45Ca]-
autoradiography; and 6) light and electron microscopic analysis of
pathologic brain specimens.

Seven-day postnatal rats will be subjected to unilateral common carotid
artery occlusion combined with exposure to 8% oxygen for varying intervals.
During the course of and following hypoxia-ischemia, the animals will be
subjected to those procedures necessary to measure regional cerebral blood
flow and metabolism as well as the evolution of the neuropathologic
alterations.  Additional studies will investigate the regional
cerebrovascular and metabolic responses of hypoxic-ischemic immature rats
subjected to: 1) hypoglycemia; 2) hyperglycemia in the recovery period and
3) therapeutic interventions, including calcium channel blockers, xanthine
oxidase inhibitors, and excitatory amino acid receptor antagonists.  It is
anticipated that the results of the proposed research will provide a more
rational basis for the management of human infants who sustain cerebral
hypoxia-ischemia (asphyxia) during the perinatal period.

## Key facts

- **NIH application ID:** 2197890
- **Project number:** 5R01HD019913-08
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **SAM.gov UEI:** TNKGNDAWB445
- **Principal Investigator:** ROBERT C. VANNUCCI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $158,590
- **Award type:** 5
- **Project period:** 1984-07-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197890

## Citation

> US National Institutes of Health, RePORTER application 2197890, PATHOGENESIS OF PERINATAL HYPOXIC-ISCHEMIC BRAIN DAMAGE (5R01HD019913-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197890. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*