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Active demyelination and neurodegeneration have been associated with early microglial and astroglial activation. While reactive microglia (MG) can contribute to tissue damage and exacerbate neurodegeneration, they also play a neuroprotective role by clearing debris through phagocytosis and secreting growth factors that support repair. The aim of this study was to evaluate the effects of MG depletion and repopulation on the response to lysophosphatidylcholine\u2010induced oligodendroglial damage using an in\u00a0vitro model previously characterized by our laboratory. Since microglial development and survival critically depend on colony\u2010stimulating factor\u20101 receptor (CSF\u20101R) signaling, we employed CSF\u20101R inhibition with BLZ945 to effectively deplete MG. Results show that repopulation occurs even in demyelinating conditions and, at early time points, results in MG exhibiting a morphology indicative of a less activated phenotype. Despite having higher phagocytic activity, early repopulating MG are few and thus unable to efficiently clear myelin debris. However, these repopulating MG still demonstrated to induce oligodendroglial differentiation. Studies using conditioned media revealed that early repopulating MG release factors into the environment which promote oligodendroglial progenitor cell viability and facilitate oligodendroglial differentiation in a demyelinating context, an effect not observed in neurons. Interestingly, our in\u00a0vitro results show a close correlation with in\u00a0vivo findings previously reported and demonstrate the relevance of our model in developing therapies for demyelinating diseases. These findings underscore both the potential and limitations of microglial modulation aimed at eliminating pro\u2010inflammatory profiles and promoting repopulation with pro\u2010regenerative characteristics.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70369-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70369","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T09:39:52Z","timestamp":1770370792000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamics and Impact of Repopulating Microglia Following Oligodendroglial Damage"],"prefix":"10.1111","volume":"170","author":[{"given":"Anabella Ayelen","family":"Di Pietro","sequence":"first","affiliation":[{"name":"Facultad de Farmacia y Bioqu\u00edmica, Departamento de Qu\u00edmica Biol\u00f3gica, C\u00e1tedra de Qu\u00edmica Biol\u00f3gica Patol\u00f3gica Universidad de Buenos Aires  Buenos Aires Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) Instituto de Qu\u00edmica y Fisicoqu\u00edmica Biol\u00f3gicas Prof. Dr. Alejandro C. 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