| First Author | Desposito D | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 9410 |
| PubMed ID | 28842604 | Mgi Jnum | J:256467 |
| Mgi Id | MGI:6108388 | Doi | 10.1038/s41598-017-09721-0 |
| Citation | Desposito D, et al. (2017) Neuroprotective effect of kinin B1 receptor activation in acute cerebral ischemia in diabetic mice. Sci Rep 7(1):9410 |
| abstractText | 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. |
