Neuroprotective effect of kinin B1 receptor activation in acute cerebral ischemia in diabetic mice

Abstract : Activation of the kallikrein-kinin system enhances cardiac and renal tolerance to ischemia. Here we investigated the effects of selective agonists of kinin B1 or B2 receptor (R) in brain ischemia-reperfusion in diabetic and non-diabetic mice. The role of endogenous kinins was assessed in tissue kallikrein deficient mice (TK−/−). Mice underwent 60min-middle cerebral artery occlusion (MCAO), eight weeks after type 1-diabetes induction. Treatment with B1R-, B2R-agonist or saline was started at reperfusion. Neurological deficit (ND), infarct size (IS), brain water content (BWC) were measured at day 0, 1 and 2 after injury. MCAO induced exaggerated ND, mortality and IS in diabetic mice. B2R-agonist increased ND and mortality to 60% and 80% in non-diabetic and diabetic mice respectively, by mechanisms involving hemodynamic failure and renal insufficiency. TK−/− mice displayed reduced ND and IS compared to wild-type littermate, consistent with suppression of B2R activity. B1R mRNA level increased in ischemic brain but B1R-agonist had no effect on ND, mortality or IS in non-diabetic mice. In contrast, in diabetic mice, B1R-agonist tested at two doses significantly reduced ND by 42–52% and IS by 66–71%, without effect on BWC or renal function. This suggests potential therapeutic interest of B1R agonism for cerebral protection in diabetes.
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Soumis le : lundi 11 septembre 2017 - 16:19:42
Dernière modification le : mercredi 13 septembre 2017 - 01:10:57

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Dorinne Desposito, Georges Zadigue, Christopher Taveau, Clovis Adam, François Alhenc-Gelas, et al.. Neuroprotective effect of kinin B1 receptor activation in acute cerebral ischemia in diabetic mice. Scientific Reports, Nature Publishing Group, 2017, 7, pp.9410. <10.1038/s41598-017-09721-0>. <hal-01585564>

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