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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 \u03b22\u2010adrenergic receptor agonist treatment drives microglial transition to a homeostatic phenotype within the post\u2010SCI 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\u2010neural circuit reparative paradigm.<\/jats:p>","DOI":"10.1002\/advs.202503966","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T08:07:53Z","timestamp":1760688473000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacological Microglial Inhibition Remodels the Scar Microenvironment to Support Reticulospinal Circuit Reconstruction After Spinal Cord Injury"],"prefix":"10.1002","volume":"13","author":[{"given":"Run","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 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