Cyclosporin A has a protective effect with induced upregulation of Hsp70 and nNOS on severe spinal cord ischemic injury in rabbits.
The purpose of this study is to ascertain the neuroprotective effect of cyclosporin A on the 25-min surgical ischemia model in the spinal cords of rabbits with neuropathological correlation and histoimmunochemical analyses measuring HSP70 and neuronal NOS (nNOS). New Zealand white rabbits were randomly divided into four groups (each n = 8): the C2, C7, Cs2, and Cs7 groups. The C2 and C7 groups underwent a 25-min surgical aortic cross-clamp without intervention and were sacrificed respectively on day 2 and on day 7 postoperatively. The Cs2 and Cs7 groups received cyclosporin A (25 mg/kg) intravenously 15 min after the 25-min cross-clamp and were sacrificed respectively on day 2 and day 7 postoperatively. Neurologic functions were evaluated on postoperative days 2 and 7 using the Tarlov scoring system. Then the rabbits were sacrificed for histopathologic observation. HSP 70 and nNOS stains with TUNEL assay were done for the C2 and Cs2 groups. All rabbits survived the experimental procedure. Tarlov's score for the Cs7 group (2.75 +/- 0.89) was significantly higher than that of the C7 group (1.25 +/- 1.39) (p < .05). Tarlov's score of the Cs7 group was also statistically higher on day 7 than on day 2 (p < .05). Strong correlation between the neurological and histological scorings was found. The TUNEL assay showed that the mean number of positive cells in the C2 group was 17.5 +/- 22.6 and in the Cs2 group was 12.5 +/- 11.1, but there was no statistically significant difference between the groups. There was more expression of HSP70 and nNOS in the cyclosporin groups than in the ischemia groups. In conclusion, this study demonstrates that cyclosporin A reduces neurological injury in the rabbit model of 25-min spinal cord ischemia. The neuroprotective effect of cyclosporin A against ischemia seems to be related to overexpressions of nNOS and HSP70.
Shin
Yoon Cheol
YC
Department of Thoracic and Cardiovascular Surgery, Kang Dong Sacred Heart Hospital, Hallym University Medical College, Seoul, Korea.
Choi
Ki Young
KY
Kim
Won Gon
WG
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D011817:Rabbits; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism; D020760:Spinal Cord Ischemia / Q000378:metabolism*; D015854:Up-Regulation
D018840:HSP70 Heat-Shock Proteins; D020011:Protective Agents; D016572:Cyclosporine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II