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• W1965162239 endingPage "8" @default.
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• W1965162239 abstract "Administration of Cyclosporin A (CsA) to rats undergoing reversible global or focal ischemia has been demonstrated to be variably neuroprotective. As CsA does not readily cross the blood–brain barrier, the variability may be due to differences in bioavailability of CsA to the ischemic brain. We have, therefore, quantitated CsA levels in blood and brain following intra-carotid injection in rats undergoing permanent right middle cerebral artery (MCA) occlusion using a three-vessel model of focal cerebral ischemia. After 30 min of three-vessel occlusion, CsA (10 mg/kg) was injected into the left external carotid artery followed by reversal of the left common carotid artery occlusion. At various times post-injection, blood samples were collected from the vena cava and samples of ischemic or sham-operated cortex were obtained for CsA quantitation by tandem mass spectrometry. Pharmacokinetic parameters were determined using non-linear mixed-effects modeling. CsA areas under the curve between normal and stroke-induced rats were not significantly different in blood (18 355 vs. 19 405 ng·h/ml, NS) or in brain tissue (15 664 vs. 14 931 ng·h/g, NS). These results demonstrate that intra-carotid injection of CsA results in high levels in brain (brain–blood ratio from 0.5 to 1). No significant differences in blood and brain exposure were observed between normal and stroke-induced rats. Therefore, reduced cerebral blood flow in the ischemic territory did not limit CsA availability to the cortex. In addition, CsA intra-carotid administration was neuroprotective following 24 h recovery as there was a significant decrease in the infarct area of the affected hemisphere compared to saline injected rats as estimated by TTC staining of viable tissue." @default.
• W1965162239 created "2016-06-24" @default.
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• W1965162239 date "2002-07-01" @default.
• W1965162239 modified "2023-10-02" @default.
• W1965162239 title "Cyclosporin A in blood and brain tissue following intra-carotid injections in normal and stroke-induced rats" @default.
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• W1965162239 doi "https://doi.org/10.1016/s0006-8993(02)02413-7" @default.
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