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Published on: March 30, 2018
Autophagy exerts a protective role in cervical spinal cord injury by microglia inhibition through the nuclear factor
1Hebei North University, Zhangjiakou, Hebei, China. richard_shaw24@126.com.
Background:
Spinal cord injury (SCI) is a serious trauma to the central nervous system. M1/M2 microglial polarization as well as the following neuroinflammatory response are crucial factors in SCI. Autophagy plays an important role in SCI, but its neuroprotective or neurodegenerative role remains controversial.
Materials And Methods:
Here, we majorly examined the properties of autophagy in SCI and uncovered the regulatory relationship between autophagy and microglial polarization in SCI.
Results:
In our study, the Basso-Beattie-Bresnahan (BBB) score was declined in SCI. The cervical contusion SCI stimulated a sustaining neuropathic pain-linked phenotype characterized by thermal hyperalgesia as well as mechanical allodynia. It was revealed the structural damage to the spinal cord in SCI. Besides, the expression of microglia markers as well as inflammatory factor were promoted in SCI. Cervical contusion SCI induced autophagy inhibition and nuclear factor kappa-B (NF-κB) activation in mice. More importantly, enhanced autophagy induced by rapamycin suppressed the NF-κB pathway and alleviated cervical contusion SCI-induced neurological function damage in mice. Additionally, rapamycin promoted microglia M2 polarization and improved microglia-mediated inflammatory response.
Conclusions:
In conclusion, our study demonstrated that autophagy played a protective role in cervical SCI by promoting microglia polarization toward M2 through the NF-κB pathway. Our study may provide a novel sight for SCI treatment.
Insights
Autophagy enhances recovery from spinal cord injury (SCI) by promoting M2 microglia polarization via the NF-κB pathway. This study reveals autophagy
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Spinal cord injury (SCI) is a severe central nervous system trauma.
- Microglial polarization (M1/M2) and neuroinflammation are key factors in SCI pathology.
- The role of autophagy in SCI, whether protective or detrimental, is debated.
Purpose of the Study:
- To investigate the role of autophagy in spinal cord injury.
- To explore the regulatory relationship between autophagy and microglial polarization in SCI.
Main Methods:
- Assessment of Basso-Beattie-Bresnahan (BBB) scores and neuropathic pain phenotypes (thermal hyperalgesia, mechanical allodynia).
- Evaluation of spinal cord structural damage, microglia marker expression, and inflammatory factors.
- Analysis of autophagy, nuclear factor kappa-B (NF-κB) activation, and rapamycin treatment effects in a mouse model of cervical contusion SCI.
Main Results:
- Cervical contusion SCI led to decreased BBB scores, neuropathic pain, structural damage, and increased microglia activation and inflammation.
- SCI induced autophagy inhibition and NF-κB activation.
- Rapamycin-enhanced autophagy suppressed NF-κB, alleviated neurological deficits, promoted M2 microglia polarization, and improved the inflammatory response.
Conclusions:
- Autophagy plays a protective role in cervical SCI.
- Autophagy promotes M2 microglia polarization through the NF-κB pathway, mitigating SCI-induced damage.
- This research offers a potential new therapeutic strategy for SCI treatment.
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