Abstract | BACKGROUND: METHODS: Thirty-six male New Zealand White rabbits were divided into the following 6 groups: group C, 15 minutes of spinal cord ischemia; group FK, FK506 (1 mg/kg) administered 30 minutes before ischemia; group CsA, cyclosporine A (30 mg/kg) administered 30 minutes before ischemia; group CsA-C, chronic administration of cyclosporine A (20 mg/kg) for 9 days before ischemia; group R, rapamycin (1 mg/kg) administered 30 minutes before ischemia; and group R+FK, rapamycin (1 mg/kg) administered 20 minutes before FK506 pretreatment (1 mg/kg). Group CsA-C was added because the drug does not readily cross the blood-brain barrier. Neurologic function was evaluated by Johnson's 5-point scale at 8, 24, and 48 hours after ischemia, and histopathology was assessed 48 hours after ischemia. RESULTS: At 24 and 48 hours after ischemia, the Johnson score was better in groups FK (4.0 +/- 1.1), R+FK (3 +/- 1.1), and CsA-C (2.7 +/- 1.2) than in group C (0.8 +/- 1.2). Numbers of morphologically intact anterior horn cells were higher in groups FK (31.3 +/- 9.9), R+FK (23.2 +/- 4.5), and CsA-C (18.3 +/- 6.8) than in group C (6.3 +/- 4.3). CONCLUSIONS:
FK506 and chronic administration of cyclosporine A, but not rapamycin, protect the spinal cord from transient ischemia. Although these results are compatible with inhibition of calcineurin in the mechanism of neuroprotective action of these drugs, other effects through different pathways cannot be excluded before further study.
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Authors | Tsuyoshi Tachibana, Norihiko Shiiya, Takashi Kunihara, Yutaka Wakamatsu, Akimaro Fabio Kudo, Tomonori Ooka, Satoshi Watanabe, Keishu Yasuda |
Journal | The Journal of thoracic and cardiovascular surgery
(J Thorac Cardiovasc Surg)
Vol. 129
Issue 1
Pg. 123-8
(Jan 2005)
ISSN: 0022-5223 [Print] United States |
PMID | 15632833
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Neuroprotective Agents
- Cyclosporine
- Sirolimus
- Tacrolimus
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Topics |
- Animals
- Ataxia
(diagnosis, epidemiology)
- Biopsy, Needle
- Cyclosporine
(pharmacology)
- Disease Models, Animal
- Drug Interactions
- Immunohistochemistry
- Male
- Neurologic Examination
- Neuroprotective Agents
(pharmacology)
- Paralysis
(diagnosis, epidemiology)
- Paraparesis
(diagnosis, epidemiology)
- Probability
- Rabbits
- Random Allocation
- Risk Factors
- Sensitivity and Specificity
- Sirolimus
(pharmacology)
- Spinal Cord Ischemia
(drug therapy, pathology, physiopathology)
- Statistics, Nonparametric
- Tacrolimus
(pharmacology)
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