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Updated: Jun 21, 2026

Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Galanin regulates M1/M2 polarization of microglia after spinal cord injury through TRPV1/Ca2+/CaMKII/NRF2 signaling
Zhongwei Zhu1, Wenjie Lu1, Yaoping Fang1
1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 32500, China; National Key Laboratory of Macromolecular Drug Development and Manufacturing, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Abstract:
Medicine strategies focused on reducing secondary injury and delaying spinal cord injury (SCI) progression by targeting M1 microglial polarization remain uncommon. Galanin (GAL), a neuroendocrine peptide, is encoded by the GAL gene. In this study, we demonstrated that administration of recombinant human GAL peptides in a mouse model of SCI significantly elevated transient receptor potential vanilloid type 1 (TRPV1) receptor expression at the injury site through GALR2, substantially alleviating inflammation during the early stages post-injury. Nuclear factor erythroid 2-related factor 2 (NRF2) is a nuclear transcription factor responsible for activating genes that protect against oxidative stress and toxicity, thereby preserving redox equilibrium. Our results indicated that GAL modulates the Ca2+/CaMKII/NRF2 signaling pathway through TRPV1, thereby suppressing the polarization of microglia towards the pro-inflammatory M1 phenotype. This modulation contributes to an improved spinal cord microenvironment and exerts neuroprotective effects following SCI. These findings underscore the therapeutic potential of GAL as an early intervention for inflammation associated with SCI.
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