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Signal."],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:p>\n                    Although reperfusion therapy effectively restores blood flow to occluded brain arteries after ischemic stroke, many patients develop persistent white matter injury, a major contributor to long-term neurological disability. Currently, there are few approved clinical therapies that specifically target white matter repair to enhance functional recovery after stroke. We demonstrated that microglial adenosine 2A receptor (A\n                    <jats:sub>2A<\/jats:sub>\n                    R) is essential for spontaneous white matter regeneration after ischemic injury in mice. Deletion of A\n                    <jats:sub>2A<\/jats:sub>\n                    R in microglia specifically impaired chronic-phase repair without altering the severity of acute ischemic injury. Pharmacological activation of A\n                    <jats:sub>2A<\/jats:sub>\n                    R signaling with blood-brain barrier\u2013permeable agonistic micelles during the early reperfusion phase enhanced white matter structural repair and led to sustained improvements in cognitive and sensorimotor function in mice. Mechanistically, A\n                    <jats:sub>2A<\/jats:sub>\n                    R activation promoted microglial efferocytosis of apoptotic cells and myelin debris in the lesioned white matter, thereby limiting secondary necrosis-induced inflammation, enhancing neurotrophic factor release, and establishing a reparative microenvironment conducive to oligodendrocyte precursor cell differentiation and remyelination. Moreover, A\n                    <jats:sub>2A<\/jats:sub>\n                    R signaling engaged HIF1\u03b1-dependent metabolic reprogramming to increase glycolysis, thereby providing the energetic support required for efficient and sustained efferocytosis. Together, these findings identify A\n                    <jats:sub>2A<\/jats:sub>\n                    R as a critical regulator of microglia-mediated white matter repair and a promising therapeutic target for enhancing regeneration after stroke.\n                  <\/jats:p>","DOI":"10.1126\/scisignal.aea4402","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:58:13Z","timestamp":1785866293000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Adenosine 2A receptor drives microglial efferocytosis to accelerate white matter repair and functional recovery after stroke"],"prefix":"10.1126","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2558-6015","authenticated-orcid":true,"given":"Yan","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Sciences, Key Laboratory of Smart Drug Delivery, Ministry of 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