2005 Volume 28 Issue 2 Pages 73-79
Objective: Traumatic Brain Injury (TBI) includes major medical, social, and economic problems. Characteristics of neuronal degeneration is biphasic manner consisiting of primary mechanical insult and progressive secondary necrosis (Sullivan et.al). Mitochondrial dysfunction is indicated as one of the important factor for TBI. However, the pathogenesis of TBI is still unknown. We previously reported that post-treatment with an immunosuppressant cyclosporin A (CsA) dramatically reduced forebrain ischemic damage in rats, and suggested the role of inhibition for both serine/threonine phosphatase 2B calcineurin and prolyl cis/trans isomerase cyclophilin D in terms of CsA related neuroprotection. However, real targets for TBI are still unknown.
Method: In this study, we performed animal experiments using rat TBI model (cold lesion model) with or without treatment of both CsA and FK506 to investigate the neuroprotective action. Especially, at the time of 1, 6, 12, 24 hours after ischemic insult, mRNA expression pattern of cortex of the hippocampus between CsA treated group and non-drug treated group were compared by microarray assay.
Result and Conclusion: Post-treatment with the immunosuppressants cyclosporin A and FK506 dramatically reduced TBI damage in rats. Analyses of expressional pattern demonstrated that expression of over 14,000 genes was changed between the groups with and without CsA treatment, and about 365 gene among them was extracted with significant difference. Further analysis disclosed that the differential expression of several gene targets showed specific patterns in a time-dependent manner.
These results may become help to elucidate the mechanisms of neuronal cell death after TBI and the CsA effect in TBI.
