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To identify and validate these mechanisms, we combined retrograde labeling, unilateral corticospinal tract injury, and spatial transcriptomics in mice, with an\n                  <jats:italic>in vitro<\/jats:italic>\n                  human neuron model of neurite regeneration. Injured corticospinal neurons (CSNs) exhibited widespread transcriptional downregulation; the few activated pathways included stress, cell death, and degenerative programs. In contrast, spared CSNs activated a coordinated pro-plasticity program characterized by metabolic, immune, and cytoskeletal remodeling together with suppression of axon growth-inhibitory signaling. Computational network and drug perturbation analyses identified, and human neuronal experiments validated,\n                  <jats:italic>ARHGEF12<\/jats:italic>\n                  suppression and the histone deacetylase inhibitor (HDAC) vorinostat as complementary target- and state-based strategies to enhance neurite regeneration. These findings define key components of endogenous plasticity and provide a framework for discovering neural repair targets.\n                <\/jats:p>","DOI":"10.64898\/2026.09.08.750239","type":"posted-content","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:15:15Z","timestamp":1789427715000},"source":"Crossref","is-referenced-by-count":0,"title":["Spared corticospinal neurons activate an endogenous plasticity program after partial CNS injury"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6391-8618","authenticated-orcid":false,"given":"Matias","family":"Murillo","sequence":"first","affiliation":[{"name":"Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06511, USA"},{"name":"Department of Neurology, Yale University School of Medicine, New Haven, CT 06511, USA"},{"name":"Department of Psychiatry, Division of Molecular Psychiatry, Wu Tsai Institute, Yale University School of Medicine, New Haven, CT 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