Necrostatin-1 Reduces Histopathology and Improves Functional Outcome after Controlled Cortical Impact in Mice

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dc.contributor.authorYou, Zerong
dc.contributor.authorSavitz, Sean I.
dc.contributor.authorYang, Jinsheng
dc.contributor.authorDegterev, Alexei
dc.contributor.authorYuan, Junying
dc.contributor.authorCuny, Gregory D.
dc.contributor.authorMoskowitz, Michael A.
dc.contributor.authorWhalen, Michael J.
dc.date.accessioned2020-03-10T17:32:19Z
dc.date.available2020-03-10T17:32:19Z
dc.date.issued2010-03
dc.description.abstractNecroptosis is a newly identified type of programmed necrosis initiated by the activation of tumor necrosis factor alpha (TNF?)/Fas. Necrostatin-1 is a specific inhibitor of necroptosis that reduces ischemic tissue damage in experimental stroke models. We previously reported decreased tissue damage and improved functional outcome after controlled cortical impact (CCI) in mice deficient in TNF? and Fas. Hence, we hypothesized that necrostatin-1 would reduce histopathology and improve functional outcome after CCI in mice. Compared with vehicle-/inactive analog-treated controls, mice administered necrostatin-1 before CCI had decreased propidium iodide-positive cells in the injured cortex and dentate gyrus (6 h), decreased brain tissue damage (days 14, 35), improved motor (days 1 to 7), and Morris water maze performance (days 8 to 14) after CCI. Improved spatial memory was observed even when drug was administered 15 mins after CCI. Necrostatin-1 treatment did not reduce caspase-3-positive cells in the dentate gyrus or cortex, consistent with a known caspase-independent mechanism of necrostatin-1. However, necrostatin-1 reduced brain neutrophil influx and microglial activation at 48 h, suggesting a novel anti-inflammatory effect in traumatic brain injury (TBI). The data suggest that necroptosis plays a significant role in the pathogenesis of cell death and functional outcome after TBI and that necrostatin-1 may have therapeutic potential for patients with TBI.
dc.identifier.citationCopyright 2008 Journal of Cerebral Blood Flow and Metabolism. This is a post-print versoin of a publiished paper that is available at: https://journals.sagepub.com/doi/full/10.1038/jcbfm.2008.44. Recommended citation: You, Zerong, Sean I. Savitz, Jinsheng Yang, Alexei Degterev, Junying Yuan, Gregory D. Cuny, Michael A. Moskowitz, and Michael J. Whalen. "Necrostatin-1 reduces histopathology and improves functional outcome after controlled cortical impact in mice." Journal of Cerebral Blood Flow & Metabolism 28, no. 9 (2008): 1564-1573. doi: 10.1038/jcbfm.2008.44. Tgia item has been deposited in accordance with publisher copyright and licensing terms and with the author's permission.
dc.identifier.urihttps://hdl.handle.net/10657/5978
dc.language.isoen_US
dc.publisherJournal of Cerebral Blood Flow and Metabolism
dc.subjectnecroptosis
dc.subjectnecrostatin
dc.subjecttraumatic brain injury
dc.subjectmice
dc.subjectnecrosis
dc.subjectinflammation
dc.titleNecrostatin-1 Reduces Histopathology and Improves Functional Outcome after Controlled Cortical Impact in Mice
dc.typeArticle

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