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Effects of Guanylate Cyclase-C on brain ischemic lesion formation (CROSBI ID 711591)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija

Ratko, Martina ; Habek, Nikola ; Dobrivojević Radmilović, Marina ; Škokić, Siniša ; Justić, Helena ; Dugandžić, Aleksandra Effects of Guanylate Cyclase-C on brain ischemic lesion formation. 2019. str. 246-246

Podaci o odgovornosti

Ratko, Martina ; Habek, Nikola ; Dobrivojević Radmilović, Marina ; Škokić, Siniša ; Justić, Helena ; Dugandžić, Aleksandra

engleski

Effects of Guanylate Cyclase-C on brain ischemic lesion formation

Aims: Agonists of guanylate cyclase (GC) A but not GC-B are reducing the size of the brain lesion after an ischemic stroke. The aim of this study is to show if GC-C is involved in development of ischemic stroke. Methods: Middle cerebral artery occlusion (MCAO) was performed in wild type (WT) and GC-C knock-out (GC-C KO) mice. The volumes of brain lesions were determined 24h and 7 days after MCAO by MRI. In addition, patch clamp experiments and immunohistochemistry were performed. Results: Twenty-four hours after MCAO, GC-C KO animals have decreased lesion volumes compared to WT mice (WT:121±12 mm3, GC-C KO:79±14 mm3). Even though we showed a reduction in brain lesion 7 days after MCAO in WT mice, there was no change in GC-C KO mice and differences between mice were not present. Furthermore, GC-C agonist, uroguanylin, hyperpolarized cerebellar Purkinje neurons, (-7.2±1.4mV, n=5) while this effect was abolished in GC-C KO mice (1.6±1.7mV, n=4). Since most of the ischemic lesion of our mouse model is located in the cerebral cortex, it is not surprising that GC-C is present in neurons of cerebral cortex. Conclusion: Effects of GC-C activation on ischemic stroke are opposite to effects of GC-A agonists. GC-C KO mice develop smaller lesion volume 24h but not 7 days after an ischemic stroke compared to WT mice suggesting the possible benefit of specific GC-C inhibitors in treatment of ischemic stroke. 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).

Guanylate cyclase-C, uroguanylin, middle cerebral artery occlusion, ischemic stroke

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Podaci o prilogu

246-246.

2019.

objavljeno

Podaci o matičnoj publikaciji

Podaci o skupu

FENS Regional Meeting

poster

10.07.2019-13.07.2019

Beograd, Srbija

Povezanost rada

Temeljne medicinske znanosti