2. Academic Validation
  3. Pharmacological Microglial Inhibition Remodels the Scar Microenvironment to Support Reticulospinal Circuit Reconstruction After Spinal Cord Injury

Pharmacological Microglial Inhibition Remodels the Scar Microenvironment to Support Reticulospinal Circuit Reconstruction After Spinal Cord Injury

  • Adv Sci (Weinh). 2025 Oct 17:e03966. doi: 10.1002/advs.202503966.
Run Li 1,  Hongyuan Xing 1,  Yifan Shen 1,  Meng Chen 2,  Bowen Lyu 1,  Xiaofeng Yang 3,  Li Sun 3,  Chao Jiang 4,  Jianyu Lv 5,  Xin Ding 6,  Zhongyang Gao 1,  Yue Wang 1
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
  • 2 M.S.E, Johns Hopkins University, 3400 North Charles Street, Hopkins, MD, 21218, USA.
  • 3 Soochow Key Laboratory of Prevention and Treatment of Child Brain injury, Children's Hospital of Soochow University, Suzhou, 215025, China.
  • 4 Department of Orthopedics, Taizhou Hospital of Zhejiang Province, Affiliated to Wenzhou Medical University, Taizhou, 317000, China.
  • 5 Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310005, China.
  • 6 Department of Neonatology, Children's Hospital of Soochow University, Suzhou, 215000, China.
PMID: 41103249 DOI: 10.1002/advs.202503966
Abstract

Due to an inhibitory scar microenvironment that prevents neural circuit reconstruction, spinal cord injury (SCI) often leads to persistent neurological dysfunction. Although neonatal murine models demonstrate that microglial inhibition enables scar remodeling to support neuroregeneration and functional recovery, effective pharmacological suppression of microglial activation in adult SCI remain elusive. Here, this work demonstrates that early β2-adrenergic receptor agonist treatment drives microglial transition to a homeostatic phenotype within the post-SCI scar. This intervention reduces inhibitory extracellular matrix deposition and transforms the inhibitory microenvironments into permissive substrates for axonal regrowth. Anatomical analyses reveal regeneration of the reticulospinal tract, which establishes synaptic connectivity with thoracolumbar circuits to mediate motor recovery in a complete SCI. These findings elucidate the therapeutic potential and neural circuit mechanisms underlying pharmacological microglial modulation for SCI repair, establishing a glial-neural circuit reparative paradigm.

Keywords

microglial inhibition; motor function recovery; reticulospinal tract; spinal cord injury; Î22‐adrenergic receptor.

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