# Investigating and treating metabolic deficits in the neurovascular unit following mild traumatic brain injury

> **NIH NIH P20** · UNIVERSITY OF KENTUCKY · 2024 · $270,481

## Abstract

Traumatic brain injuries (TBIs) are a major societal and public health concern with over 1.7 million TBIs,
~80% of which mild, are reported each year in the US. TBI is also a major risk factor for dementias and
Alzheimer’s Disease. Mild TBI is characterized by dysfunction of the neurovascular unit (NVU), initiated by
breakdown of the blood-brain barrier and followed by synaptic dyshomeostasis. Mitochondrial dysfunction is
apparent in the NVU after mild TBI, accompanied by metabolic imbalance and oxidative damage. This project
will examine the metabolic deficits of distinct components of the NVU, including neuronal synapse and brain
capillaries, by using steady state metabolomics as well as intra-mitochondrial metabolic tracing following mild
TBI. These results will be generated in conjunction with profiling of mitochondrial bioenergetics of the NVU
components. These studies will directly use the resources provided by the CNS-Met Metabolomics Core. P7C3-
A20, which elevates NAD+ and demonstrates efficacy in TBI models, will be administered alongside nicotinamide
mononucleotide, which is a NAD+ precursor, to examine therapeutic effect at restoring alterations in metabolism
and functional outcomes. The completion of these studies will generate an enhanced understanding of
mitochondrial dysfunction and metabolite flux in distinct components of the NVU following mild TBI and provide
supportive data on a pathology-modifying drugs targeting NAD+ to treat this disease.

## Key facts

- **NIH application ID:** 10841480
- **Project number:** 5P20GM148326-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** William Brad Hubbard
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $270,481
- **Award type:** 5
- **Project period:** 2023-05-15 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841480

## Citation

> US National Institutes of Health, RePORTER application 10841480, Investigating and treating metabolic deficits in the neurovascular unit following mild traumatic brain injury (5P20GM148326-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10841480. Licensed CC0.

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