# Strategy to Potentiate Rehabilitation after TBI

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $584,976

## Abstract

Abstract
Metabolic depression (MD) occurs during the acute period of TBI and this impairs the ability of neuronal circuits
to meet local activity demand, which in turn could limit the success of rehabilitative strategies, and functional
outcome. Although most neurons survive mild or moderate TBI, at least acutely, they cannot operate efficiently
and this severely compromises brain function, which may lead to persistent behavioral deficits. This manifests
as a loss of correlated functional activity using resting state functional magnetic resonance imaging (rsFMRI)
and is typically reported using a connectomic analysis of brain network function. There remains much to learn
about how to treat the injured brain, how the functional trajectory of neurons evolves with time, and the
dependence on the extent and major pathologic subtype of the initial injury. We propose combined rsFMRI,
behavior and molecular studies of metabolism and synaptic plasticity that will provide a longitudinal analysis of
injury to investigate how MD manifests in altered functional connectivity and brain reorganization chronically. We
will use the information gained to provide insight on how the small molecule agonist of TrkB receptors - 7,8-
dihydroxyflavone (DHF) will alter the functional trajectory of the injured brain through reduction of MD acutely,
followed by enhancement of synaptic plasticity and cognitive outcome chronically. By modelling clinical situations
of early post-injury rehabilitation versus rehabilitation that is delayed due to additional injuries, we will determine
whether an intervention with DHF will mitigate the effects of acute MD, followed by, or simultaneously with the
reinstitution of function using a period of early or delayed exercise. We propose studies that will test whether
either intervention, alone or in combination, can be delayed but still provide a significant boost to brain
connectivity and functional outcome. We will conduct these studies in both male and female rats, and will use
new statistically-driven methods that provide a level of confidence to enable subject-level analysis for
discrimination of burden of tissue damage, regardless of the actual injury severity. We will employ these
covariates of MD, tissue swelling and atrophy, as well as exercise level, to derive a statistically robust analysis
of whether off-setting MD acutely, will potentiate the effects of rehabilitation.

## Key facts

- **NIH application ID:** 10749916
- **Project number:** 5R01NS116383-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Fernando Gomez-Pinilla
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $584,976
- **Award type:** 5
- **Project period:** 2020-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10749916

## Citation

> US National Institutes of Health, RePORTER application 10749916, Strategy to Potentiate Rehabilitation after TBI (5R01NS116383-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10749916. Licensed CC0.

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