Early and delayed neuroprotective effects of FK506 on experimental focal ischemia quantitatively assessed by diffusion-weighted MRI

• Published in: Magnetic resonance imaging Vol. 19; no. 2; pp. 153 - 160
• Main Authors: EBISU, T, KATSUTAD, K, FUJIKAWA, A, AOKI, I, UMEDA, M, NARUSE, S, TANAKA, C
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 01.02.2001
• Subjects: Animals; Biological and medical sciences; Brain - drug effects; Brain - pathology; Diffusion; Image Enhancement; Image Processing, Computer-Assisted; Infarction, Middle Cerebral Artery - pathology; Injections, Intravenous; Investigative techniques, diagnostic techniques (general aspects); Magnetic Resonance Imaging; Male; Medical sciences; Nervous system; Neurology; Neuroprotective Agents - pharmacology; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Rats; Rats, Sprague-Dawley; Reperfusion Injury - pathology; Tacrolimus - pharmacology; Vascular diseases and vascular malformations of the nervous system; Animal model; Nervous system diseases; Rat; Treatment efficiency; Rodentia; Cardiovascular disease; Experimental study; Nuclear magnetic resonance imaging; Waiting time; Cerebral disorder; Vascular disease; Vertebrata; Mammalia; Cytoprotector; Ischemia; Tacrolimus; Animal; Immunotherapy; Central nervous system disease; Diffusion coefficient; Cerebrovascular disease; Monitoring; Brain (vertebrata)
• ISSN: 0730-725X; 1873-5894
• DOI: 10.1016/S0730-725X(01)00233-8

The immunosuppressive drug FK506 (tacrolimus) has been reported to be a powerful neuroprotective agent in the focal ischemia of animals. However, no report has been published concerning neuroprotective effect of this compound on the morphology in superacute stage. The separate analysis between early and delayed effects of FK506 on the morphology may be helpful in the study of the compound's mechanism of action which is still unknown. The goal of this study was to determine early and delayed effects of pharmacological treatment with FK506 in permanent MCA occlusion using magnetic resonance imaging (MRI). Nineteen rats were subjected to permanent MCA occlusion, and given either intravenous injection of placebo or 1 mg/kg FK506 immediately after occlusion. DWI and T(2)-weighted MRI were performed 3 and 24 h after MCA occlusion, and postmortem histological analysis was also performed. FK506 drastically reduced the ischemic damage in 3-h apparent diffusion coefficient (ADC) map. This is the first report to demonstrate the neuroprotective effects of FK506 on focal cerebral ischemia in superacute stage. In addition, postmortem ischemic damage tended to be smaller than ischemic area indicated by 3-h ADC map in the FK506 group, whereas there was an excellent equality between them in the placebo group, suggesting the possible effect of FK506 on the later ischemic period. Our findings provide direct evidence for the neuroprotective effect of FK506 on ischemic cell damage in both early stage and possibly later stage.