MP Resulting in Autophagic Cell Death of Microglia through Zinc Changes against Spinal Cord Injury
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Updated: Mar 22, 2026
Identifying Microglia and Peripheral Infiltrating Macrophages in the Injured Spinal Cords Using Flow Cytometry
Published on: June 24, 2025
Dingding Li1, Guannan Wang2, Donghe Han3
1Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
Abstract:
Methylprednisolone pulse therapy (MPPT), as a public recognized therapy of spinal cord injury (SCI), is doubted recently, and the exact mechanism of MP on SCI is unclear. This study sought to investigate the exact effect of MP on SCI. We examined the effect of MP in a model of SCI in vivo and an LPS induced model in vitro. We found that administration of MP produced an increase in the Basso, Beattie, and Bresnahan scores and motor neurons counts of injured rats. Besides the number of activated microglia was apparently reduced by MP in vivo, and Beclin-1 dependent autophagic cell death of microglia was induced by MP in LPS induced model. At the same time, MP increases cellular zinc concentration and level of ZIP8, and TPEN could revert effect of MP on autophagic cell death of microglia. Finally, we have found that MP could inhibit NF-κβ in LPS induced model. These results show that the MP could result in autophagic cell death of microglia, which mainly depends on increasing cellular labile zinc, and may be associated with inhibition of NF-κβ, and that MP can produce neuroprotective effect in SCI.
Insights
Methylprednisolone pulse therapy (MPPT) enhances recovery from spinal cord injury (SCI) by inducing microglial autophagic cell death. This mechanism involves increased cellular zinc and may inhibit NF-κβ signaling, offering neuroprotection.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Methylprednisolone pulse therapy (MPPT) is a recognized treatment for spinal cord injury (SCI).
- The precise mechanism of MP's action in SCI remains unclear.
- Recent studies question the efficacy and underlying mechanisms of MPPT.
Purpose of the Study:
- To elucidate the exact effects and molecular mechanisms of methylprednisolone (MP) on spinal cord injury (SCI).
- To investigate MP's impact on neuroprotection and microglial cell death pathways.
Main Methods:
- In vivo SCI rat model and in vitro LPS-induced microglial model were utilized.
- Assessment of motor function (Basso, Beattie, and Bresnahan scores) and motor neuron counts.
- Analysis of microglial activation, autophagic cell death (Beclin-1 dependent), cellular zinc levels (ZIP8, TPEN), and NF-κβ signaling.
Main Results:
- MP administration improved motor function and motor neuron counts in SCI rats.
- MP reduced activated microglia in vivo and induced Beclin-1 dependent autophagic cell death in vitro.
- MP increased cellular zinc and ZIP8 levels, an effect reversible by TPEN.
- MP inhibited NF-κβ signaling in the LPS-induced model.
Conclusions:
- MP induces autophagic cell death in microglia, primarily by increasing cellular labile zinc.
- This process may be associated with NF-κβ inhibition, contributing to MP's neuroprotective effects in SCI.
- MP demonstrates potential neuroprotective benefits in spinal cord injury through novel mechanisms.
