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  • 标题:Nitric oxide synthase mediates cerebellar dysfunction in mice exposed to repetitive blast-induced mild traumatic brain injury
  • 本地全文:下载
  • 作者:Aric F. Logsdon ; Abigail G. Schindler ; James S. Meabon
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2020
  • 卷号:10
  • 期号:1
  • 页码:1-14
  • DOI:10.1038/s41598-020-66113-7
  • 出版社:Springer Nature
  • 摘要:We investigated the role of nitric oxide synthase (NOS) in mediating blood-brain barrier (BBB) disruption and peripheral immune cell infiltration in the cerebellum following blast exposure. Repetitive, but not single blast exposure, induced delayed-onset BBB disruption (72 hours 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 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 (24–71 hours 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.
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