# Cardiolipin as a Novel Target for Neuroprotection after Spinal Cord Injury

> **NIH VA I01** · RLR VA MEDICAL CENTER · 2020 · —

## Abstract

Spinal cord injury (SCI) is among the most disabling conditions affecting wounded members of the U.S. military.
Unfortunately, there has been no effective treatment available for SCI patients. It is, therefore, an urgent
medical need to develop novel repair strategies to mitigate the devastating nature of SCI and to translate them
clinically to improve quality of life of our veterans with SCI. Recently, a novel lipid signaling pathway, namely
the cardiolipin (CL)-cytochrome c pathway, that control cell death/apoptosis has been identified. CL is a
structurally unique dimeric phospholipid localized in the inner mitochondrial membrane where it is required for
optimal mitochondrial function. CL is a preferred oxidation substrate in neuronal injury, is the only phospholipid
in the mitochondria that undergoes early oxidation during apoptosis, and is an early target of reactive oxygen
species (ROS) attack. Alteration of CL has been associated with mitochondrial dysfunction in a variety of
pathological conditions. Using mass spectrometry-based lipidomics for the first time in SCI, we have generated
preliminary data showing CL peroxidation and loss after SCI. Remarkably, XJB-5-131 (XJB),  a novel
mitochondria-targeted antioxidant, administered at 30 min post-SCI significantly reduces tissue damage and
improves behavioral recovery in adult rats. These data strongly suggest that CL alteration is a key mechanism
that mediates injury-induced cell death and tissue damage. However, the role and mechanism of CL alteration
in SCI remain unclear. Here, we hypothesize that CL alteration, including peroxidation and loss, is a central
process that mediates spinal cord secondary injury, and that restoration of CL level may lead to
neuroprotection and recovery of function after SCI. Using a rat spinal cord neuronal culture system in vitro and
an adult rat thoracic contusive SCI model in vivo, we will determine 1) whether CL alteration induces
mitochondrial dysfunction and neuronal death and whether such detrimental effects can be reversed by a novel
mitochondrial targeted antioxidant XJB; 2) the molecular role of CL alteration in the signaling pathway of
neuronal apoptosis after SCI and whether such CL alteration is sufficient to mediate secondary SCI; 3) whether
abnormal mitochondrial dynamics also play a role in CL alteration-mediated cell death; and 4) an optimal dose
and therapeutic time window of XJB on neuroprotection and functional recovery after rat contusive SCI.

## Key facts

- **NIH application ID:** 9859332
- **Project number:** 5I01BX003705-03
- **Recipient organization:** RLR VA MEDICAL CENTER
- **Principal Investigator:** XIAO-MING XU
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859332

## Citation

> US National Institutes of Health, RePORTER application 9859332, Cardiolipin as a Novel Target for Neuroprotection after Spinal Cord Injury (5I01BX003705-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9859332. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*