Rabbits brain ischemia

In studies conducted in the 1960s in a model of complete brain ischemia in rabbits, it was shown that the duration of tolerable ischemia compatible with complete functional and histological recovery increased continuously with declining temperature, and could be extended fivefold by reducing temperature from 37°C to 25°C (18). Other workers showed that a decrease of body temperature of only 1-3°C reduced the degree of brain energy metabolite depletion and acidosis in a model of carotid ligation and hypoxia (19). 

We established a cerebral ischemia-reperfusion model using rabbits because the well-developed cerebral collateral circulation seen in rabbits makes this model closer to the human system than models using mice or rats as the test species. The rabbit cerebral ischemia-reperfusion model was made by transorbital occlusion of the right carotid, middle cerebral, and anterior cerebral arteries for 2.5 h followed by a release of occlusion for reperfusion (49). Moreover, an anti-IL-8 mAb also reduced hemorrhagic and edematous changes observed in reperfused rabbit brain. 

High antioxidative activity carvedilol has been shown in isolated rat heart mitochondria [297] and in the protection against myocardial injury in postischemic rat hearts [281]. Carvedilol also preserved tissue GSL content and diminished peroxynitrite-induced tissue injury in hypercholesterolemic rabbits [298]. Habon et al. [299] showed that carvedilol significantly decreased the ischemia-reperfusion-stimulated free radical formation and lipid peroxidation in rat hearts. Very small I50 values have been obtained for the metabolite of carvedilol SB 211475 in the iron-ascorbate-initiated lipid peroxidation of brain homogenate (0.28 pmol D1), mouse macrophage-stimulated LDL oxidation (0.043 pmol I 1), the hydroxyl-initiated lipid peroxidation of bovine pulmonary artery endothelial cells (0.15 pmol U1), the cell damage measured by LDL release (0.16 pmol l-1), and the promotion of cell survival (0.13 pmol l-1) [300]. SB 211475 also inhibited superoxide production by PMA-stimulated human neutrophils. 

In this model, we examined the production of IL-8 in brain tissue. IL-8 was barely detectable in brain tissue from sham-operated rabbits. Ischemic treatment of the brain alone did not increase IL-8 levels in brain tissue even though ischemia lasted for 14.5 h. However, reperfusion for 6 h significantly increased IL-8 contents in brain tissue without significant elevation of IL-8 levels in plasma, suggesting a local production of IL-8 in reperfused brain tissues. Immunohistochemically, IL-8 protein was detected mainly in the perivascular neutrophils and vascular walls in brains reperfused longer than 6 h. These locally produced IL-8 may be responsible for the severe neutrophil extravasation in the reperfused brain. 

Fig. 2 In vivo MRI of rabbit ischemic brain that received mesenchymal stem cells labeled with chitosan-SPION. Asterisk indicates ischemic area and open arrows indicate chitosan-SPION-labeled mesenchymal stem cells at the injection site, (a, b) T2WI and diffusion weighted image (DWI) of brain immediately after injection of mesenchymal stem cell at contralateral side of ischemic area (open arrows) on day 4 of ischemia, (c, d) T2WI and susceptibility weighted image (SWI) 16 days after stem cell transplantation. At the ischemic site, dark signal (white arrows) on SWI matches mesenchymal stem cells (black arrows) on Prussian staining (e, f)- (e. 0 Prussian blue staining detected iron-labeled stem cells at the liquefied infarct area in a section of 4% paraformaldehyde-fixed brain tissue tut day 16. Reprinted fiom [92] by permission fi om The Korean Academy of Medical Sciences, Journal of Korean Medical Science. Copyright 2010...

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