{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:01:43Z","timestamp":1783652503614,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS131756"],"award-info":[{"award-number":["NS131756"]}],"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":[[2025,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Approximately 20% of familial cases of amyotrophic lateral sclerosis (ALS) are caused by mutations in the gene encoding superoxide dismutase 1 (SOD1). Epidemiological data have identified traumatic brain injury (TBI) as an exogenous risk factor for ALS; however, the mechanisms by which TBI may worsen SOD1 ALS remain largely undefined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We sought to determine whether repetitive TBI (rTBI) accelerates disease onset and progression in the transgenic SOD1<jats:sup>G93A<\/jats:sup> mouse ALS model, and whether loss of the primary regulator of axonal degeneration sterile alpha and TIR motif containing 1 (<jats:italic>Sarm1<\/jats:italic>) mitigates the histological and behavioral pathophysiology. We subjected wild\u2010type (n\u2009=\u200923), <jats:italic>Sarm1<\/jats:italic> knockout (KO; n\u2009=\u200917), SOD1<jats:sup>G93A<\/jats:sup> (n\u2009=\u200919), and SOD1<jats:sup>G93A<\/jats:sup>xSarm1<jats:sup>KO<\/jats:sup> (n\u2009=\u200926) mice of both sexes to rTBI or sham surgery at age 64\u2009days (62\u201368\u2009days). Body weight and ALS\u2010deficit score were serially assessed up to 17\u2009weeks after surgery and histopathology assessed in layer V of the primary motor cortex at the study end point.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In sham injured SOD1<jats:sup>G93A<\/jats:sup> mice, genetic ablation of <jats:italic>Sarm1<\/jats:italic> did not attenuate axonal loss, improve neurological deficits, or survival. The rTBI accelerated onset of G93A\u2010SOD1 ALS, as indicated by accentuated body weight loss, earlier onset of hindlimb tremor, and shortened survival. The rTBI also triggered TDP\u201043 mislocalization, enhanced axonal and neuronal loss, microgliosis, and astrocytosis. Loss of <jats:italic>Sarm1<\/jats:italic> significantly diminished the impact of rTBI on disease progression and rescued rTBI\u2010associated neuropathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>SARM1\u2010mediated axonal death pathway promotes pathogenesis after TBI in SOD1<jats:sup>G93A<\/jats:sup> mice suggesting that anti\u2010SARM1 therapeutics are a viable approach to preserve neurological function in injury\u2010accelerated G93A\u2010SOD1 ALS. ANN NEUROL 2025;97:963\u2013975<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.27174","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T05:38:27Z","timestamp":1736487507000},"page":"963-975","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic Ablation of <i>Sarm1<\/i> Mitigates Disease Acceleration after Traumatic Brain Injury in the <scp>SOD1<sup>G93A<\/sup><\/scp> Transgenic Mouse Model of Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","volume":"97","author":[{"given":"Elif O.","family":"Dogan","sequence":"first","affiliation":[{"name":"Department of Neurology University of Massachusetts Chan Medical School  Worcester MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean R.","family":"Simonini","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Massachusetts Chan Medical School  Worcester 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