{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:58:14Z","timestamp":1788951494163,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T00:00:00Z","timestamp":1721433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["W81XWH2110597"],"award-info":[{"award-number":["W81XWH2110597"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS128080"],"award-info":[{"award-number":["NS128080"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Despite the high prevalence, mild traumatic brain injury (mTBI)\u2010induced chronic headache and cognitive deficits are poorly understood and lack effective treatments. Low\u2010dose interleukin\u20102 (LD\u2010IL\u20102) treatment soon after mTBI or overexpressing IL\u20102 in brain astrocytes prior to injury protects mice from developing post\u2010traumatic headache (PTH)\u2010related behaviors and cognitive decline. The present study addresses a clinically relevant knowledge gap: whether LD\u2010IL\u20102 treatment long after the initial injury is still effective for chronic PTH and cognitive deficits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>mTBI was induced by a noninvasive closed\u2010head weight drop method. LD\u2010IL\u20102 was administered 4\u20136\u2009weeks post\u2010mTBI to assess its effects on chronic PTH\u2010related facial mechanical hypersensitivity as well as mTBI\u2010induced impairment in novel object recognition and object location tests. Endogenous regulatory T (Treg) cells were depleted to investigate the mechanism of action of LD\u2010IL\u20102.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Delayed LD\u2010IL\u20102 treatment abolished chronic PTH\u2010related behaviors. It also completely reversed mTBI\u2010induced cognitive impairment in both male and female mice. Treg cell depletion not only prolonged PTH\u2010related behaviors but also abolished the effects of LD\u2010IL\u20102. Interestingly, LD\u2010IL\u20102 treatment significantly increased the number of Treg cells in dura but not in brain tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These results suggest that the beneficial effects of LD\u2010IL\u20102 treatment are mediated through the expansion of meningeal Treg cells. Collectively, our study identifies Treg as a cellular target and LD\u2010IL\u20102 as a promising therapy for both chronic PTH and mTBI\u2010induced cognitive impairment for both males and females, with a wide therapeutic time window and the potential of reducing polypharmacy in mTBI treatment. 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