{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:58:29Z","timestamp":1790618309672,"version":"4.1.0"},"reference-count":120,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Central nervous system (CNS) injury remains a severe neurological condition with limited regenerative capacity. NG2\u2010glia are abundant and functionally versatile glial cells that have attracted increasing attention in CNS repair research. However, their roles are complex and context\u2010dependent, ranging from early pathological involvement to later reparative potential, and a systematic synthesis of this temporal dichotomy is lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We systematically searched PubMed and Web of Science from inception to 2026 using combinations of keywords including \u201cNG2\u2010glia,\u201d \u201cNG2 cells,\u201d \u201coligodendrocyte precursor cells,\u201d \u201cOPCs,\u201d and \u201cCNS injury.\u201d Additional references were identified by manual screening of reference lists. We prioritized mechanistic and therapeutic studies published within the last 10\u2009years, while foundational discoveries were included for historical context.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>This review establishes that NG2\u2010glia exhibit a time\u2010dependent dual role after CNS injury. In the early stage (hours to days), they rapidly proliferate, migrate to the lesion, and secrete chondroitin sulfate proteoglycans (CSPGs), forming a chemical and physical barrier that inhibits axonal regeneration and may facilitate neuropathic pain. In the middle\u2010to\u2010late stages (days to weeks\/months), they shift toward repair functions, including remyelination via differentiation into oligodendrocytes, neuronal trans\u2010differentiation (primarily under forced reprogramming), and anti\u2010inflammatory\/neuroprotective effects through interactions with microglia, astrocytes, and neurons. Their fate is determined by intrinsic factors (age, heterogeneity) and extrinsic microenvironmental signals (damage\u2010associated molecules, cytokines, and signaling pathways such as Wnt\/\u03b2\u2010catenin and TGF\u2010\u03b22). Therapeutically, diverse strategies\u2014including CB1 receptor agonists to promote remyelination, chondroitinase ABC to neutralize CSPG inhibition, and SOX2\/NeuroD1\u2010based reprogramming to generate functional neurons\u2014have shown preclinical promise, yet significant translational gaps remain, including poor endogenous neurogenesis, constitutive differentiation limitations, and safety concerns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Perspective<\/jats:title>\n                    <jats:p>Targeting NG2\u2010glia offers a novel avenue for CNS repair, but successful interventions must be precisely timed and stage\u2010specific rather than unregulated promotion or inhibition. This review proposes an analytical framework of \u201ctime\u2010dependent dual roles\u201d to reconcile the contradictory functions of NG2\u2010glia and highlights critical future directions, including deciphering regional heterogeneity, elucidating the molecular switches that govern state transitions, validating the functional integration of reprogrammed neurons, and bridging the bench\u2010to\u2010bedside divide. A deeper understanding of the regulatory logic underlying NG2\u2010glia plasticity will inform next\u2010generation precision therapies for CNS injuries.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71162","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:57:21Z","timestamp":1789480641000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>NG2<\/scp>\n                    \u2010Glia in Central Nervous System Following Injury: From Pathological Involvement to Repair Potential"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7831-0936","authenticated-orcid":false,"given":"Yunyun","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology Medical School of Nantong University, Co\u2010Innovation Center of Neuroregeneration  Nantong Jiangsu 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