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Updated: Jan 31, 2026

Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion Injury
Qiang Li1, Shane Gao2, Zhanrong Kang3
1Department of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
The spinal cord is extremely vulnerable to ischemia-reperfusion (I/R) injury, and the mitochondrion is the most crucial interventional target. Rapamycin can promote autophagy and exert neuroprotective effects in several diseases of the central nervous system. However, the impact of rapamycin via modulating mitophagy and apoptosis after spinal cord ischemia-reperfusion injury remains unclear. This study was undertaken to investigate the potential role of rapamycin in modulating mitophagy and mitochondria-dependent apoptosis using the spinal cord ischemia-reperfusion injury (SCIRI) mouse model. We found that rapamycin significantly (p < 0.05) enhanced mitophagy by increasing the translocation of p62 and Parkin to the damaged mitochondria in the mouse spinal cord injury model. At the same time, rapamycin significantly (p < 0.05) decreased mitochondrial apoptosis related protein (Apaf-1, Caspase-3, Caspase-9) expression by inhibiting Bax translocation to the mitochondria and the release of the cytochrome c from the mitochondria. After 24 h following SCIRI, rapamycin treatment reduced the TUNEL+ cells in the spinal cord ischemic tissue and improved the locomotor function in these mice. Our results therefore demonstrate that rapamycin can improve the locomotor function by promoting mitophagy and attenuating SCIRI -induced apoptosis, indicating its potential therapeutic application in a spinal cord injury.
Insights
Rapamycin enhances mitophagy and reduces apoptosis in spinal cord injury models. This neuroprotective effect improves locomotor function, suggesting rapamycin as a potential therapy for spinal cord injury.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Spinal cord ischemia-reperfusion (I/R) injury poses a significant threat to the central nervous system.
- Mitochondria are key targets in I/R injury.
- Rapamycin's neuroprotective potential via autophagy is recognized, but its role in spinal cord injury-induced mitophagy and apoptosis is unclear.
Purpose of the Study:
- To investigate rapamycin's effect on mitophagy and mitochondria-dependent apoptosis in a mouse model of spinal cord ischemia-reperfusion injury (SCIRI).
Main Methods:
- Utilized a SCIRI mouse model.
- Assessed mitophagy by measuring p62 and Parkin translocation to damaged mitochondria.
- Evaluated mitochondrial apoptosis by analyzing Apaf-1, Caspase-3, Caspase-9 expression, Bax translocation, and cytochrome c release.
- Quantified TUNEL-positive cells and assessed locomotor function 24 hours post-SCIRI.
Main Results:
- Rapamycin significantly enhanced mitophagy, evidenced by increased p62 and Parkin translocation.
- Rapamycin significantly reduced mitochondrial apoptosis markers, inhibiting Bax translocation and cytochrome c release.
- Rapamycin treatment decreased TUNEL-positive cells and improved locomotor function in SCIRI mice.
Conclusions:
- Rapamycin promotes mitophagy and attenuates SCIRI-induced apoptosis.
- Rapamycin improves locomotor function following spinal cord injury.
- Rapamycin demonstrates potential as a therapeutic agent for spinal cord injury.
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