# Metabolic Mechanisms of Recovery in Mild TBI

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2024 · $628,133

## Abstract

Project Summary
The occurrence of concussion, or mild TBI, has been steadily increasing in incidence over the past decade.
One possible consequence of concussion - post-concussion syndrome - can persist for weeks to months and
result in life dissatisfaction for the patient and economic burden for society. With the development of new
rodent models for mild TBI, we can now study the molecular mechanisms that mediate injury and/or protection
from a single TBI. Our previous work identified significant changes in the guanine deaminase cytosolic PSD-95
interactor (cypin) after mild and moderate TBI, and in turn, discovered small molecule cypin activators that are
neuroprotective in vitro and restore neurocognition in vivo in both mild and moderate TBI models. Cellular
concentrations of methionine, a key metabolic effector that regulates neurocognition, increases shortly after
mild TBI, and our preliminary data point to cypin as a pivotal molecule for restoring methionine levels to
baseline after TBI. We are proposing that activation of purine metabolism by cypin attenuates methionine
levels via two mechanisms: 1) by altering cellular metabolism needed for methionine production and 2) by
binding to adenosylhomocysteinase like 1 (AHCYL1), sequestering it from inhibiting adenosylhomocysteinase,
allowing the methionine cycle to continue and reducing methionine accumulation post-mTBI. These
mechanisms can be harnessed for therapeutic application. Our proposed work determines whether the
activation of cypin can be targeted after mild TBI to promote functional recovery in mice. Broadly, our proposed
experiments will identify new molecular targets for treating TBI patients and reducing the long-term morbidity of
TBI on society.

## Key facts

- **NIH application ID:** 10979265
- **Project number:** 1R01NS135406-01A1
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** BONNIE L FIRESTEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $628,133
- **Award type:** 1
- **Project period:** 2024-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979265

## Citation

> US National Institutes of Health, RePORTER application 10979265, Metabolic Mechanisms of Recovery in Mild TBI (1R01NS135406-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10979265. Licensed CC0.

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