# Role and Function of Peroxisomal Ether Phospholipids in TBI

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $424,875

## Abstract

PROJECT SUMMARY
 Traumatic brain injury (TBI) is one of the major health concern affecting almost 1.7 million annually in the
US. To date no effective therapy is available, mainly because of incomplete understanding of the molecular
mechanisms of injury associated biochemical changes in the injured brain. In this study we aim to determine
the role and function of ether phospholipids in neurodegeneration after TBI. Ether phospholipids play crucial
role in maintaining structural integrity and protecting cellular membrane from oxidative stress. Their synthesis is
initiated by the enzyme machinery of peroxisomes. Decreased level of ether phospholipids due to impaired
peroxisomal functions have been demonstrated in different neurodegenerative diseases. However, their role in
the pathophysiology of TBI has not been assessed. In this study our goal is to test the hypothesis that
dysregulation of ether phospholipid abundance due to the impairment in peroxisomal ether phospholipid
synthesis contributes to neuronal death after TBI.
 We will use liquid chromatography mass spectrometry (LC-MS/MS) based lipidomic approach to determine
the changes in ether phospholipids in the whole cortical tissues of TBI mice. We will also determine the levels of
ether phospholipid precursors in the peroxisomal fractions isolated from mouse cortices after TBI to assess
peroxisomal ether phospholipid synthesizing function in the injured cortices. We will also use in vitro neuronal
stretch injury model to investigate the mechanisms of dysregulation in ether phospholipid abundance and its role
in neuronal death after injury. In AIM 1, we will investigate the mechanisms of dysregulation in ether
phospholipid and its role in neuronal death after TBI in mice. LC-MS/MS based lipidomic analysis combined
with biochemical methods will be used to test the hypothesis that peroxisomal ether phospholipid synthesis is
impaired in the mouse brain after TBI causing decrease in ether phospholipid abundance that contributes to
neuronal death in the injured brain. In AIM 2, we will determine the neuroprotective functions of ether
phospholipid precursor supplementation in TBI mice. We hypothesize that increase in ether phospholipid
abundance will attenuate injury associated neuronal death and will restore motor and cognitive functions in TBI
mice. We will treat TBI mice with ether phospholipid precursor – 1-O-alkyl glycerol and assess its neuroprotective
functions by measuring the extent of neuronal death and functional recovery in those mice.
 Our study will for the first time determine the role and function of ether phospholipids in TBI. We believe
that this study will provide new mechanistic insight about TBI associated neuronal death and thus may help us
to identify novel therapeutic target to treat TBI.

## Key facts

- **NIH application ID:** 10218660
- **Project number:** 1R21NS117867-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Jace W Jones
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $424,875
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218660

## Citation

> US National Institutes of Health, RePORTER application 10218660, Role and Function of Peroxisomal Ether Phospholipids in TBI (1R21NS117867-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10218660. Licensed CC0.

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