Comparative neuroprotective effects of cyclosporin A and NIM811, a nonimmunosuppressive cyclosporin A analog, following traumatic brain injury.

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
L H MbyeE D Hall

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 i...Continue Reading

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Methods Mentioned

BETA
protein assay
electrophoresis
Infrared Imaging

Software Mentioned

Neuroscore
Image
Pro Plus
Statview
Statistica

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Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.