Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
J Cereb Blood Flow Metab ; 29(1): 87-97, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18714331

ABSTRACT

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.


Subject(s)
Brain Injuries/prevention & control , Cyclosporine/chemistry , Cyclosporine/pharmacology , Neuroprotective Agents/pharmacology , Animals , Brain Injuries/metabolism , Brain Injuries/pathology , Calpain/metabolism , Cytoskeleton/drug effects , Cytoskeleton/enzymology , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/pharmacology , Male , Mice , Motor Activity/drug effects , Neuroprotective Agents/chemistry , Physical Conditioning, Animal , Spectrin/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...