2. Academic Validation
  3. A critical role for microglia in regulating metabolic homeostasis and neural repair after spinal cord injury

A critical role for microglia in regulating metabolic homeostasis and neural repair after spinal cord injury

  • Free Radic Biol Med. 2024 Nov 20:225:469-481. doi: 10.1016/j.freeradbiomed.2024.10.288.
Huan Jian 1,  Kailin Wu 1,  Yigang Lv 1,  Jiawei Du 1,  Mengfan Hou 1,  Chi Zhang 2,  Jianqing Gao 3,  Hengxing Zhou 4,  Shiqing Feng 5
Affiliations

Affiliations

  • 1 Department of Orthopaedics, Tianjin Medical University General Hospital, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin, China.
  • 2 Department of Orthopaedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong University Center for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
  • 3 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. Electronic address: [email protected].
  • 4 Department of Orthopaedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong University Center for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China. Electronic address: [email protected].
  • 5 Department of Orthopaedics, Tianjin Medical University General Hospital, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin, China; Department of Orthopaedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong University Center for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Department of Orthopedics, The Second Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. Electronic address: [email protected].
PMID: 39413980 DOI: 10.1016/j.freeradbiomed.2024.10.288
Abstract

Traumatic spinal cord injury (SCI) often results in severe immune and metabolic disorders, aggravating neurological damage and inhibiting locomotor functional recovery. Microglia, as resident immune cells of the spinal cord, play crucial roles in maintaining neural homeostasis under physiological conditions. However, the precise role of microglia in regulating immune and metabolic functions in SCI is still unclear and is easily confused with that of macrophages. In this study, we pharmacologically depleted microglia to explore the role of microglia after SCI. We found that microglia are beneficial for the recovery of locomotor function. Depleting microglia disrupted glial scar formation, reducing neurogenesis and angiogenesis. Using liquid chromatography tandem mass spectrometry (LC‒MS/MS), we discovered that depleting microglia significantly inhibits lipid metabolism processes such as fatty acid degradation, unsaturated fatty acid biosynthesis, glycophospholipid metabolism, and sphingolipid metabolism, accompanied by the accumulation of multiple organic acids. Subsequent studies demonstrated that microglial depletion increased the inhibition of FASN after SCI. FASN inhibition exacerbated malonyl-CoA accumulation and significantly impeded the activity of mTORC1. Moreover, microglial depletion exacerbated the oxidative stress of neurons. In summary, our results indicate that microglia alleviate neural damage and metabolic disorders after SCI, which is beneficial for achieving optimal neuroprotection and neural repair.

Keywords

Metabolism; Microglia; Oxidative stress; Spinal cord injury; mTORC1.

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