Comparative Neuroprotective Effects of Cyclosporin a and NIM811, a Nonimmunosuppressive Cyclosporin a Analog, following Traumatic Brain Injury

DOI Web Site Web Site 被引用文献3件
  • Lamin Han Mbye
    Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, Kentucky, USA
  • Indrapal N Singh
    Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, Kentucky, USA
  • Kimberly M Carrico
    Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, Kentucky, USA
  • Kathryn E Saatman
    Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, Kentucky, USA
  • Edward D Hall
    Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, Kentucky, USA

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公開日
2008-08-20
権利情報
  • https://journals.sagepub.com/page/policies/text-and-data-mining-license
DOI
  • 10.1038/jcbfm.2008.93
公開者
SAGE Publications

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説明

<jats:p>Earlier experiments have shown that cyclosporin A (CsA) and its non-calcineurin inhibitory analog NIM811 attenuate mitochondrial dysfunction after experimental traumatic brain injury (TBI). Presently, we compared the neuroprotective effects of previously determined mitochondrial protective doses of CsA (20 mg/kg intraperitoneally) and NIM811 (10 mg/kg intraperitoneally) when administered at 15 mins postinjury in preventing cytoskeletal (α-spectrin) degradation, neuro-degeneration, and neurological dysfunction after severe (1.0 mm) controlled cortical impact (CCI) TBI in mice. In a first set of experiments, we analyzed calpain-mediated α-spectrin proteolysis at 24 h postinjury. Both NIM811 and CsA significantly attenuated the increased α-spectrin breakdown products observed in vehicle-treated animals ( P < 0.005). In a second set of experiments, treatment of animals with either NIM811 or CsA at 15 mins and again at 24 h postinjury attenuated motor function impairment at 48 h and 7 days ( P < 0.005) and neurodegeneration at 7 days postinjury ( P < 0.0001). Delayed administration of NIM811 out to 12 h was still able to significantly reduce α-spectrin degradation. These results show that the neuroprotective mechanism of CsA involves maintenance of mitochondrial integrity and that calcineurin inhibition plays little or no role because the non-calcineurin inhibitory analog, NIM811, is as effective as CsA.</jats:p>

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