assessing-microglial-phagocytosis-myelin-debris-vitro-under-repeated

Assessing Microglial Phagocytosis of Myelin Debris <em>in vitro</em> Under Repeated Magnetic Stimulation

Microglia, the resident phagocytes of the central nervous system (CNS), play a pivotal role in maintaining CNS integrity and homeostasis by removing ...

The First Affiliated Hospital of Nanjing Medical University

Spinal cord injury (SCI) is a serious trauma of the central nervous system. The clearance of myelin debris is a critical step in the functional recovery following spinal cord injury (SCI). Recent studies have begun to reveal critical roles for professional phagocytes in the central nervous system, microglia, and their receptors in the control of myelin debris in neurodegenerative disease. Repeated trans-spinal magnetic stimulation (rTSMS) has been demonstrated as a noninvasive SCI treatment that enhances tissue repair and functional recovery. In this study, we investigated the role and molecular mechanism of rTSMS on microglial phagocytosis of myelin debris in a rat SCI model. In our studies, we found that rTSMS significantly promoted the motor function recovery of SCI rats associated with the inhibition the neuroinflammation and glia scar formation. Immunofluorescence results further showed that the rTSMS promotes the clearance of myelin debris by microglia in vivo and in vitro. Additionally, receptor-associated protein (RAP), a Low-density lipoprotein receptor-related protein-1 (LRP-1) inhibitor, could cancel the accelerated microglial phagocytosis of myelin debris after rTSMS in vitro experiments. Simultaneously, Elisa's results and western blotting respectively showed that rTSMS significantly decreased the levels of soluble LRP-1(sLRP-1) and the LRP-1 splicing enzyme of ADAM17. In conclusion, rTSMS could promote the clearance of myelin debris by microglia through LRP-1 to improve the functional recovery of SCI rats.

Repeated trans-spinal magnetic stimulation promotes microglial phagocytosis of myelin debris after spinal cord injury through LRP-1.

Spinal cord injury is followed by glial scar formation, which was long seen mainly as a physical barrier preventing axonal regeneration. Glial scar astrocytes lead to glial scar formation and produce inhibitory factors to prevent axons from growing through the scar, while inhibiting the conversion of reactive astrocytes into glial scar-forming astrocytes may represent an ideal treatment for CNS injury. Exercise is a non-invasive and effective therapeutic intervention for clinical rehabilitation of spinal cord injury. However, its precise therapeutic mechanisms still need to be continuously explored.

Body weight-supported treadmill training reduces glial scar overgrowth in SCI rats by decreasing the reactivity of astrocytes during the subacute phase.

Current treatments for neuropathic pain are suboptimal, necessitating the search for more effective therapeutics. Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effects, and focal repetitive trans-spinal magnetic stimulation showed an anti-neuroinflammatory effect in spinal cord injury rat models. Here, we speculated that repetitive trans-spinal magnetic stimulation might induce an anti-inflammatory effect to alleviate neuropathic pain by upregulating calmodulin-dependent protein kinase kinase beta (CaMKKβ)/adenosine 5'-monophosphate-activated protein kinase (AMPK)/suppressor of cytokine signaling-3 (SOCS3) signaling in microglia. Experiments have found that non-invasive focal repetitive trans-spinal magnetic stimulation effectively alleviates mechanical allodynia and spinal neuroinflammation in rats with neuropathic pain induced by chronic sciatic nerve ligation. Further research found that repetitive trans-spinal magnetic stimulation upregulated the expression of SOCS3 in spinal microglia, which subsequently inhibited the phosphorylation of p38 mitogen-activated protein kinase and signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 nuclear translocation in rats with neuropathic pain, thereby suppressing neuroinflammation. The upregulation of SOCS3 by repetitive trans-spinal magnetic stimulation may be achieved through the activation of the CaMKKβ/AMPK signaling pathway in microglia. The results suggested that local repetitive trans-spinal magnetic stimulation inhibits spinal neuropathy and alleviates neuropathic pain by activating the CaMKKβ/AMPK/SOCS3 signaling pathway in spinal microglia. This mechanism provides an effective noninvasive treatment for neuropathic pain caused by spinal cord injury.

Article	Year
Repeated trans-spinal magnetic stimulation promotes microglial phagocytosis of myelin debris after spinal cord injury through LRP-1. Experimental neurology\| PubMed ID: 38830500	2024
Body weight-supported treadmill training reduces glial scar overgrowth in SCI rats by decreasing the reactivity of astrocytes during the subacute phase. BMC neuroscience\| PubMed ID: 40295901	2025
Trans-spinal magnetic stimulation attenuates neuropathic pain caused by spinal cord injury. Neural regeneration research\| PubMed ID: 40313090	2025

Jili Cai

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