Abstract
Cell death is a key issue in spinal cord secondary injury. Ferroptosis is recently discovered as an iron-dependent type of cell death that is distinct from other forms of cell death pathways such as apoptosis and necrosis. This research is aimed to investigate the role of ferroptosis in spinal cord injury (SCI) pathophysiology, and to explore the effectiveness of ferroptosis inhibitor on SCI. We examined the ferroptosis markers and the factors in a rat contusion SCI model. Seen from transmission electron microscopy (TEM) following SCI, mitochondria showed ferroptotic characteristic changes. Treatment with a ferroptosis inhibitor SRS 16-86 enhanced functional recovery after SCI through the upregulation of anti-ferroptosis factor GPX4, GSH and xCT, and the downregulation of the lipid peroxidation marker 4HNE. SRS 16-86 treatment alleviated astrogliosis and enhanced neuronal survival after SCI. The inflammatory cytokine levels (IL-1β, TNF-α and ICAM-1) were decreased significantly post SRS 16-86 treatment after SCI. These findings suggest strong correlation between ferroptosis and the secondary injury of SCI. The effectiveness of ferroptosis inhibitor SRS-16-86 on SCI repair leads to the identification of a novel therapeutic target for SCI.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 48-57 |
| Number of pages | 10 |
| Journal | Brain Research |
| Volume | 1706 |
| DOIs | |
| State | Published - Mar 1 2019 |
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Keywords
- Ferroptosis
- Ferroptosis inhibitor
- GPX4
- Regulated cell death
- Secondary injury
- Spinal cord injury
ASJC Scopus subject areas
- Neuroscience(all)
- Molecular Biology
- Clinical Neurology
- Developmental Biology
Cite this
Ferroptosis inhibitor SRS 16-86 attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury. / Zhang, Yan; Sun, Chao; Zhao, Chenxi; Hao, Jian; Zhang, Yiling; Fan, Baoyou; Li, Bo; Duan, Huiquan; Liu, Chang; Kong, Xiaohong; Wu, Ping; Yao, Xue; Feng, Shiqing.
In: Brain Research, Vol. 1706, 01.03.2019, p. 48-57.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ferroptosis inhibitor SRS 16-86 attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury
AU - Zhang, Yan
AU - Sun, Chao
AU - Zhao, Chenxi
AU - Hao, Jian
AU - Zhang, Yiling
AU - Fan, Baoyou
AU - Li, Bo
AU - Duan, Huiquan
AU - Liu, Chang
AU - Kong, Xiaohong
AU - Wu, Ping
AU - Yao, Xue
AU - Feng, Shiqing
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Cell death is a key issue in spinal cord secondary injury. Ferroptosis is recently discovered as an iron-dependent type of cell death that is distinct from other forms of cell death pathways such as apoptosis and necrosis. This research is aimed to investigate the role of ferroptosis in spinal cord injury (SCI) pathophysiology, and to explore the effectiveness of ferroptosis inhibitor on SCI. We examined the ferroptosis markers and the factors in a rat contusion SCI model. Seen from transmission electron microscopy (TEM) following SCI, mitochondria showed ferroptotic characteristic changes. Treatment with a ferroptosis inhibitor SRS 16-86 enhanced functional recovery after SCI through the upregulation of anti-ferroptosis factor GPX4, GSH and xCT, and the downregulation of the lipid peroxidation marker 4HNE. SRS 16-86 treatment alleviated astrogliosis and enhanced neuronal survival after SCI. The inflammatory cytokine levels (IL-1β, TNF-α and ICAM-1) were decreased significantly post SRS 16-86 treatment after SCI. These findings suggest strong correlation between ferroptosis and the secondary injury of SCI. The effectiveness of ferroptosis inhibitor SRS-16-86 on SCI repair leads to the identification of a novel therapeutic target for SCI.
AB - Cell death is a key issue in spinal cord secondary injury. Ferroptosis is recently discovered as an iron-dependent type of cell death that is distinct from other forms of cell death pathways such as apoptosis and necrosis. This research is aimed to investigate the role of ferroptosis in spinal cord injury (SCI) pathophysiology, and to explore the effectiveness of ferroptosis inhibitor on SCI. We examined the ferroptosis markers and the factors in a rat contusion SCI model. Seen from transmission electron microscopy (TEM) following SCI, mitochondria showed ferroptotic characteristic changes. Treatment with a ferroptosis inhibitor SRS 16-86 enhanced functional recovery after SCI through the upregulation of anti-ferroptosis factor GPX4, GSH and xCT, and the downregulation of the lipid peroxidation marker 4HNE. SRS 16-86 treatment alleviated astrogliosis and enhanced neuronal survival after SCI. The inflammatory cytokine levels (IL-1β, TNF-α and ICAM-1) were decreased significantly post SRS 16-86 treatment after SCI. These findings suggest strong correlation between ferroptosis and the secondary injury of SCI. The effectiveness of ferroptosis inhibitor SRS-16-86 on SCI repair leads to the identification of a novel therapeutic target for SCI.
KW - Ferroptosis
KW - Ferroptosis inhibitor
KW - GPX4
KW - Regulated cell death
KW - Secondary injury
KW - Spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=85055648132&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055648132&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2018.10.023
DO - 10.1016/j.brainres.2018.10.023
M3 - Article
VL - 1706
SP - 48
EP - 57
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -