# INTERACTION OF HYPOXIC AND EXCITOTOXIC NEURONAL INJURY

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 1991 · $151,850

## Abstract

This proposal examines the relationship between hypoxic neuronal damage
and glutamate (GLU) neurotoxicity.  An hypoxic-ischemic episode, as might
occur focally during stroke or cerebral hemorrhage or globally during
cardiac arrest, results in the accumulation of external GLU and
neurodegeneration.  It is unknown if hypoxia-induced neuronal lysis
liberates excessive GLU or if metabolically compromised, intact neurons
release GLU which then exerts further toxic effects.  A detailed
hypothesis is presented to explain the elevations of intracellular free
calcium ion (Cal) and accumulation of endogenous GLU following metabolic
compromise.  In this model, eventual toxicity results from the enhanced
deleterious effects GLU rather than the initial hypoxia.  Combinations of
hypoxic insult and exogenously applied GLU are expected to produce
additive, or supraadditive, effects in this scheme.  Experiments are
proposed to measure survival of dissociated, hippocampal neurons
maintained in a tissue culture environment after individual and combined
exposure to excitatory amino acids (EAA), oxygen deprivation, and sodium
cyanide (NaCN) as a model of "chemical hypoxia".  Additional measurements
will be made of resting and altered levels of Cal and intracellular pH
(pH1) to determine involvement of these ions in the response to toxic
insult and in the signal pathway leading to neuronal death.  Methods are
proposed for documenting the release of endogenous glutamate after
hypoxic insult.  Surviving neurons will be examined for their
physiological responses to EAA and for the presence or absence of
specific cytoplasmic calcium-binding proteins to identify cellular
processes possibly conferring resistance to toxic insults.

## Key facts

- **NIH application ID:** 3122003
- **Project number:** 1R01AG010034-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **SAM.gov UEI:** C3KXNLTAAY98
- **Principal Investigator:** JANET M DUBINSKY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $151,850
- **Award type:** 1
- **Project period:** 1991-08-01 → 1994-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122003

## Citation

> US National Institutes of Health, RePORTER application 3122003, INTERACTION OF HYPOXIC AND EXCITOTOXIC NEURONAL INJURY (1R01AG010034-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122003. Licensed CC0.

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