# Polyamine and Glutamate Driven Interactions in the Glioblastoma-Brain Microenvironment

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $340,669

## Abstract

Project Summary
Radiotherapy is a standard modality for brain lesions, and has led improvements in patient outcome through
the addition of high precision stereotactic delivery and more recently particle therapy. While patients are
benefiting from increasing survival times, cognitive complications develop with increased frequency and are
thus challenging treatment paradigms. Biologically, the mechanisms of neurotoxicity from ionizing radiation
are unclear. Recent studies have highlighted exquisite sensitivity to an organ that has been traditionally
thought to be radioresistant due to its non-proliferative nature. Dendrite remodeling, neuroinflammation, and
excitotoxicity are all elevated following exposure to ionizing radiation, and are thought to contribute to
decreased cognition. In the current application, we propose that excessive glutamate signaling is a key driver
of cognitive damage from radiation. In addition, our group has been investigating the role of the polyamine
pathway in radiation resistance of tumor cells. Both glutamate and polyamines are found to be elevated in
brain tumors, an induced secretion is evident after exposure to radiation. In mechanistic studies, we implicate
the NMDAR NR2B subunit as a specific target of glutamate and polyamines that leads to neurotoxicity. We
hypothesize that blocking glutamate-receptor signaling with a specific glutamate receptor antagonist will
reduce CNS damage due to radiation, and sensitize tumor cells to radiation induced death, and therefore
improve patient outcomes.

## Key facts

- **NIH application ID:** 10692574
- **Project number:** 5R01CA187053-08
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Scott Michael Welford
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $340,669
- **Award type:** 5
- **Project period:** 2015-08-07 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10692574

## Citation

> US National Institutes of Health, RePORTER application 10692574, Polyamine and Glutamate Driven Interactions in the Glioblastoma-Brain Microenvironment (5R01CA187053-08). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10692574. Licensed CC0.

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