| Autor: |
Mbye LH; Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA., Singh IN, Carrico KM, Saatman KE, Hall ED |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism [J Cereb Blood Flow Metab] 2009 Jan; Vol. 29 (1), pp. 87-97. Date of Electronic Publication: 2008 Aug 20. |
| DOI: |
10.1038/jcbfm.2008.93 |
| Abstrakt: |
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 (alpha-spectrin) degradation, neurodegeneration, 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 alpha-spectrin proteolysis at 24 h postinjury. Both NIM811 and CsA significantly attenuated the increased alpha-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 alpha-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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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