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Updated: Dec 6, 2025
Spinal Cord Neurons Isolation and Culture from Neonatal Mice
Published on: July 11, 2017
MCC950 Reduces Neuronal Apoptosis in Spinal Cord Injury in Mice
Ning He1, Xiaohe Zheng1, Teng He1
1Department of Basic Medicine Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Background:
Traumatic Spinal Cord Injury (SCI) is a severe condition usually accompanied by an inflammatory process that gives rise to uncontrolled local apoptosis and a subsequent unfavorable prognosis. One reason for this unfavorable outcome could be the activation of the NLRP3 inflammasome.
Objective:
MCC950 is a specific inhibitor of NLRP3 that further inhibits the formation of the NLRP3 inflammasome. The purpose of this study was to determine whether the NLRP3 inflammasome was associated with the severity of local apoptosis and whether MCC950 could prevent neuronal apoptosis following SCI.
Methods:
In this study, primary cortical neurons were cultured in vitro. With or without pretreatment/ posttreatment with MCC950, neurons were subjected to Oxygen-Glucose Deprivation (OGD) for 2 h and then reperfusion for 20 h. Immunofluorescence was used to determine the expression of NLRP3, ASC, and cleaved caspase-1 in neurons. In vivo, SCI model mice were established with a 5 g weight-drop method. MCC950 was intraperitoneally injected at 0, 2, 4, 6, 8, 10, and 12 days after SCI. Basso Mouse Scale (BMS) scores and footprint assays were used to assess motor function. Paw withdrawal threshold and tail-flick latency were used to assess somatosensory function. H&E, Nissl, and TUNEL staining were used to measure histological changes and apoptosis at 3 days after SCI, and scar formation was observed by Masson staining and GFAP immunohistochemical analysis at 28 days after SCI.
Results:
Immunofluorescence analysis confirmed that MCC950 inhibited OGD-induced activation of the NLRP3 inflammasome in neurons. Behavioral tests, Masson staining, and GFAP immunohistochemical analysis showed that MCC950-treated mice had improved neuronal functional recovery and reduced scar formation at 28 days after SCI. H&E, Nissl, and TUNEL staining confirmed that there were more living neurons and fewer apoptotic neurons in MCC950-treated mice than control mice at 3 days after SCI.
Conclusion:
These results reveal that MCC950 exerts neuroprotective effects by reducing neuronal apoptosis, preserving the survival of the remaining neurons, attenuating the severity of the damage, and promoting the recovery of motor function after SCI.
Insights
MCC950, an inhibitor of the NLRP3 inflammasome, reduces neuronal apoptosis and promotes functional recovery after spinal cord injury (SCI). This study demonstrates MCC950
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Traumatic spinal cord injury (SCI) involves inflammation and neuronal apoptosis, leading to poor outcomes.
- NLRP3 inflammasome activation is a key contributor to this detrimental process.
- Understanding the role of NLRP3 inflammasome in SCI pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the association between NLRP3 inflammasome activation and the severity of neuronal apoptosis post-SCI.
- To evaluate the neuroprotective potential of MCC950, a specific NLRP3 inhibitor, in preventing neuronal apoptosis and promoting functional recovery after SCI.
Main Methods:
- In vitro: Primary cortical neurons subjected to oxygen-glucose deprivation (OGD) with or without MCC950 treatment; immunofluorescence used to assess NLRP3 inflammasome components.
- In vivo: SCI mouse model induced by weight-drop; MCC950 administered intraperitoneally; motor and sensory function assessed using BMS scores, footprint assays, paw withdrawal threshold, and tail-flick latency.
- Histological analysis: H&E, Nissl, TUNEL, Masson staining, and GFAP immunohistochemistry used to evaluate neuronal survival, apoptosis, and scar formation.
Main Results:
- MCC950 effectively inhibited OGD-induced NLRP3 inflammasome activation in neurons.
- MCC950 treatment in SCI mice led to improved motor and sensory functional recovery.
- Histological analysis revealed reduced neuronal apoptosis and scar formation in MCC950-treated mice compared to controls.
Conclusions:
- MCC950 demonstrates significant neuroprotective effects following spinal cord injury.
- The drug reduces neuronal apoptosis, enhances survival of existing neurons, and mitigates damage severity.
- MCC950 promotes motor function recovery, highlighting its therapeutic potential for SCI.
