# Mechanisms of metabolic adaptation after traumatic brain injury

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $358,203

## Abstract

PROJECT SUMMARY / ABSTRACT
Traumatic brain injury (TBI) results in life-long cognitive and motor disabilities. TBI elicits acute and
prolonged metabolic adaptations in an attempt to provide physiological fuel and to enable the survival
of damaged nervous tissue. The overall objective of this proposal is to determine the mechanisms of
metabolic adaptation to injury and the metabolic requirements that promote recovery following TBI.
The pathophysiology of TBI is complex and characterized largely by dysregulated glucose
metabolism. However, brain contains high concentration of fatty acids, which are liberated from
plasma membrane following TBI and further propagate secondary injury by promoting inflammation
and lipid peroxidation. We have shown that brain is capable of utilizing these fatty acids for energy
and metabolism via β-oxidation. Specifically, this mechanism is present in neural progenitor cells and
astrocytes. Thus, this mechanism allows to re-direct fatty acids to mitochondria for β-oxidation.
Importantly, our preliminary data show that fatty acid oxidation is increased following traumatic brain
injury. We hypothesize that the injured brain requires the up-regulation of fatty acid oxidation
specifically in astrocytes in order to spare glucose for neurons as well as eliminating toxic fatty acid
intermediates following damage to nervous tissue and blood brain barrier. Using tissue specific
transgenic and knockout mouse models, we will test this hypothesis and detail these fundamental
unanswered questions. To test these hypothesis we propose three specific aims: 1) Determine the
spatial and temporal contribution of brain fatty acid metabolism following TBI; 2) Determine the
requirement for brain fatty acid oxidation following TBI; 3) Determine the requirements for systemic
metabolic adaptations following TBI. The long-term goal of this project is to determine the regulation
and requirement for fatty acid oxidation pathway following TBI. Thus, these studies will elucidate how
fatty acid metabolism is regulated following the injury and advance our understanding of metabolic
adaptations. Furthermore, the fundamental knowledge how fatty acid metabolism is altered after TBI
could lead to targeted therapies to improve brain energy and metabolism after neurological insult.
!

## Key facts

- **NIH application ID:** 10336385
- **Project number:** 5R01NS111230-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Susanna Scafidi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $358,203
- **Award type:** 5
- **Project period:** 2019-02-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10336385

## Citation

> US National Institutes of Health, RePORTER application 10336385, Mechanisms of metabolic adaptation after traumatic brain injury (5R01NS111230-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10336385. Licensed CC0.

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