Related Experiment Video
Updated: Jan 24, 2026
Paradigms of Lower Extremity Electrical Stimulation Training After Spinal Cord Injury
Published on: February 1, 2018
RIP3 inhibition protects locomotion function through ameliorating mitochondrial antioxidative capacity after spinal
Yang Wang1, Jianhang Jiao1, Shanyong Zhang1
1Department of Orthopedics, the Second Hospital of Jilin University, Changchun, 130041, China.
Abstract:
A novel type of programmed necrosis called necroptosis has been identified in the field of cell death, thereby offering an opportunity for re-examining necrosis after spinal cord injury (SCI). Several recent studies have suggested receptor-interacting protein kinase 3 (RIP3) plays an important role in necrosis in many cell types. However, it is still unclear what downstream events that lead to cell death are triggered by RIP3 activation. Hence, link between RIP3 inhibition and induction of neuronal cell death via mitochondrial function and antioxidative capacity after SCI was studied in our work. We examined the protective effects of RIP3 inhibition in SCI-mice. Furthermore, mimicking the pathological conditions of SCI in vitro, spinal cord neurons were subjected to oxygen-glucose deprivation. Notably, we found GSK872 and Nec-1 ameliorated the locomotor function and spinal cord edema, and conferred reverse of SCI-induced loss of mitochondrial integrity, ATP, glutathione and superoxide dismutase and elevation of reactive oxygen species and malonyldialdehyde in SCI-mice. Moreover, GSK872 alleviated OGD-inducted mitochondrial dysfunction, decreased antioxidative capacity and cell death in spinal cord neurons, through inhibiting RIP3 activity. The data suggest improving antioxidative capacity as a potential multifunctional treatment after SCI and the broader possibility of targeting RIP3 activity as a therapeutic window for spinal neuroprotective intervention.
Insights
Inhibiting receptor-interacting protein kinase 3 (RIP3) activity protects against spinal cord injury (SCI) by improving mitochondrial function and antioxidant capacity. This suggests RIP3 inhibition as a potential therapeutic strategy for neuroprotection after SCI.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Necroptosis, a programmed necrosis, is a novel cell death pathway relevant to spinal cord injury (SCI).
- Receptor-interacting protein kinase 3 (RIP3) is implicated in necrosis, but its downstream effects in SCI are not fully understood.
- Understanding RIP3's role is crucial for developing neuroprotective strategies after SCI.
Purpose of the Study:
- To investigate the neuroprotective effects of RIP3 inhibition in a mouse model of SCI.
- To determine the impact of RIP3 inhibition on mitochondrial function and antioxidant capacity following SCI.
- To explore RIP3 inhibition as a potential therapeutic target for SCI.
Main Methods:
- Administered RIP3 inhibitors (GSK872, Nec-1) to SCI mice and evaluated locomotor function and spinal cord edema.
- Assessed mitochondrial integrity, ATP levels, and antioxidant markers (glutathione, superoxide dismutase) in SCI mice.
- Utilized an in vitro oxygen-glucose deprivation model of SCI using spinal cord neurons to study GSK872 effects on mitochondrial dysfunction, antioxidant capacity, and cell death.
Main Results:
- RIP3 inhibition (GSK872, Nec-1) significantly improved locomotor function and reduced spinal cord edema in SCI mice.
- Treatment reversed SCI-induced mitochondrial damage, restored ATP levels, and enhanced antioxidant defenses (glutathione, superoxide dismutase).
- GSK872 mitigated oxygen-glucose deprivation-induced mitochondrial dysfunction, reduced antioxidant capacity, and decreased neuronal cell death by inhibiting RIP3.
Conclusions:
- RIP3 inhibition demonstrates significant neuroprotective effects in both in vivo and in vitro models of SCI.
- Targeting RIP3 activity can restore mitochondrial integrity and enhance antioxidative capacity, crucial for recovery after SCI.
- Enhancing antioxidative capacity and targeting RIP3 represent promising therapeutic avenues for spinal neuroprotection.
Related Concept Videos
01:26Spinal Cord
01:54The Spinal Cord
01:10Spinal Cord: Information Processing
Sensory Information Processing
Sensory information processing begins at the sensory receptors located in the skin and other tissues, which detect somatic sensory stimuli such as touch, temperature, or pain. These receptors function as catalysts, initiating...
01:15Spinal Cord: Gross Anatomy
01:47Lung Capacity
02:59Animal Mitochondrial Genetics