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Repetitive, but not single blast exposure, induced delayed-onset BBB disruption (72\u2009hours post-blast) in cerebellum. The NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) administered after blast blocked BBB disruption and prevented CD4<jats:sup>+<\/jats:sup> T-cell infiltration into cerebellum. L-NAME also blocked blast-induced increases in intercellular adhesion molecule-1 (ICAM-1), a molecule that plays a critical role in regulating blood-to-brain immune cell trafficking. Blocking NOS-mediated BBB dysfunction during this acute\/subacute post-blast interval (24\u201371\u2009hours after the last blast) also prevented sensorimotor impairment on a rotarod task 30 days later, long after L-NAME cleared the body. In postmortem brains from Veterans\/military Servicemembers with blast-related TBI, we found marked Purkinje cell dendritic arbor structural abnormalities, which were comparable to neuropathologic findings in the blast-exposed mice. Taken collectively, these results indicate that blast provokes delayed-onset of NOS-dependent pathogenic cascades that can later emerge as behavioral dysfunction. These results also further implicate the cerebellum as a brain region vulnerable to blast-induced mTBI.<\/jats:p>","DOI":"10.1038\/s41598-020-66113-7","type":"journal-article","created":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T10:03:15Z","timestamp":1591783395000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Nitric oxide synthase mediates cerebellar dysfunction in mice exposed to repetitive blast-induced mild traumatic brain injury"],"prefix":"10.1038","volume":"10","author":[{"given":"Aric F.","family":"Logsdon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail G.","family":"Schindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Meabon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Yagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie J.","family":"Herbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Banks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray A.","family":"Raskind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desiree A.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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