Curcumin-activated Olfactory Ensheathing Cells Improve Functional Recovery After Spinal Cord Injury by Modulating Microglia Polarization Through APOE/TREM2/NF-κB Signaling Pathway

Journal of Neuroimmune Pharmacology, 2023 · DOI: 10.1007/s11481-023-10081-y · Published: September 2, 2023

Spinal Cord Injury Pharmacology Neurology

Simple Explanation

Spinal cord injury (SCI) often leads to irreversible motor deficits and sensory dysfunction. Neural repair is difficult due to neuron properties and a hostile environment (inflammation, ischemia, hypoxia and glial scars) after SCI. Inflammatory responses greatly contribute to the severity of SCI, making it necessary to develop strategies to regulate pathophysiological processes and improve the microenvironment. Cellular therapy can be an effective option to ameliorate SCI pathologies. This study explores the effects of transplanting curcumin-activated olfactory ensheathing cells (aOECs) on neural regeneration in rats after SCI. The results indicated that aOECs promoted neurological function recovery by shifting microglia from M1 to M2.

Study Duration

Not specified

Participants

60 Sprague Dawley (SD) female rats

Evidence Level

Not specified

Key Findings

1
CCM-activated OECs effectively attenuated deleterious inflammation by regulating microglia polarization from the pro-inflammatory (M1) to anti-inflammatory (M2) phenotype in SCI rats and facilitated functional recovery after SCI.
2
Microglial polarization to M2 elicited by aOECs-CM in LPS-induced microglia was effectively reversed when TREM2 expression was downregulated.
3
CCM-activated OECs could alleviate inflammation after SCI by switching microglial polarization from M1 to M2, which was likely mediated by the APOE/TREM2/NF-κB pathway, and thus ameliorated neurological function.

Research Summary

This study found that aOECs could attenuate inflammatory response by regulating microglia from pro-inflammatory to anti-inflammatory phenotype in SCI rats, thus facilitating functional recovery. The study demonstrated that aOECs played a favorable role in modulating LPS-induced microglia polarization to M2 through TREM2/NF-κB. CCM significantly elevated APOE production from OECs, which actively contributes to the cell events.

Practical Implications

Therapeutic Potential

The use of CCM-activated OECs presents a novel therapeutic approach for treating SCI by modulating microglia polarization and reducing inflammation.

Molecular Pathway Targeting

The APOE/TREM2/NF-κB signaling pathway is identified as a key mechanism, suggesting potential targets for pharmacological interventions to enhance recovery after SCI.

Cell-Based Therapy Enhancement

Activating OECs with CCM could improve the efficacy of cell-based therapies for SCI by boosting their anti-inflammatory and neuroprotective functions.

Study Limitations

1
M1/M2 phenotypes were defined based on classic markers, rather than a broader gene array analysis.
2
TREM2 may have impacts on other signaling pathways besides NF-κB.
3
Other transcription factors can also participate in regulating NF-κB activity.

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