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The role of multiple glial cell types in driving major RBI pathologies remains largely unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The late-phase radiation response in mouse brain was profiled and analyzed using bulk tissue RNA-sequencing and single-nucleus mRNA sequencing (snRNA-seq). Glia crosstalk was investigated by using primary culture and co-culture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found substantial loss of mature oligodendrocytes and microglia-derived neuroinflammation as 2 major features in late phase of RBI. Loss of oligodendrocytes coincides with the emergence of a radiation-induced reactive microglial subpopulation (RRM_1) characterized by enhanced phagocytosis activity, specialized for myelin debris clearance. Myelin debris phagocytosis induces a M2-to-M1 phenotypic transition in irradiated microglia. Astrocyte-microglia lactate shuttle (AMLS), mediated by monocarboxylate transporters (MCT4\/MCT1), suppresses M1-like polarization of microglia. M2-like phenotype could be enhanced by secreted secreted phosphoprotein 1 (SPP1) via boosting AMLS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Taken together, we found demyelination and neuroinflammation are two intimately related features in irradiated brain. Microglia and astrocyte collectively contribute to tissue homeostasis by stably scavenging myelin\/cellular debris. Our data reveal a correlative glial metabolic cascade (oligodendrocytes, microglia, and astrocytes) linked to chronic neuroinflammation. These findings provide new insights into therapeutic strategies for RBI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/noajnl\/vdag215","type":"journal-article","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T12:50:49Z","timestamp":1786798249000},"source":"Crossref","is-referenced-by-count":0,"title":["Astrocyte-microglia lactate shuttle restrains microglial phenotypic transition during myelin phagocytosis in radiation-induced brain injury"],"prefix":"10.1093","volume":"8","author":[{"given":"Rong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University , Guangzhou, Guangdong Province,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anbang","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Guangzhou Institute of Cancer Research, the Affiliated 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