engleski

The role of Guanylate Cyclase-C on ischemic stroke

INTRODUCTION: Stroke has been identified as one of the leading causes of mortality in industrializes countries. Natriuretic peptides are involved in different physiological and patophophysiological conditions in the brain. Agonists of guanylate cyclase A but not B lead to decrease of brain lesion size after middle cerebral occlusion (MCAO). Therefore, uroguanylin (UGN) and its receptor guanylate cyclase C (GC-C), could also play a role in development of brain lesions and edema after ischemic injury. AIM: The purpose of this study is to describe the role of GC-C and its agonist, UGN, in the development of ischemic stroke in the murine model of ischemia. METHODS: MCAO was performed in wild type (WT), GC- C and UGN knock-out (GC-C -/-, UGN -/-) mice. Lesion volumes were measured 1 and 7 days after stroke and correlated to neurological impairment test scores. RESULTS: GC-C -/- animals show a significant reduction in lesion volumes 1 day after MCAO compared to their WT counterparts, whose lesion volume diminishes 7 days after MCAO. However, UGN -/- animals developed similar lesion volumes and oedema size 1 day after MCAO as their wild-type littermates (UGN +/+). CONCLUSION: Our results show that the activation of GC-C could lead to an increase in lesion volume following ischemic stroke. The difference in stroke volume is visible 1 day after MCAO, and is only present in GC-C-/- and not in UGN -/- animals. This difference could indicate GC-C activation by another agonist or the existence of an GC-C independent signalling pathway. ACKNOWLEDGEMENTS Research was funded by the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience (project “Experimental and clinical research of hypoxic-ischemic damage in perinatal and adult brain” ; GA KK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund) and Croatian Science Foundation project BRADISCHEMIA (UIP-2017-05-8082).

middle cerebral artery occlusion, uroguanylin, MR imaging

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