Naslov
Effects of uroguanylin's signalling pathway on ischemic stroke

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

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
FENS Forum 2022

Mjesto i datum
Pariz, FRancuska, 09.07.2022. - 13.07.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
urogvanilin, gvanilat ciklaza C, ishemijski moždani udar
(uroguanylin, guanylate cyclase C, ischemic stroke)

Sažetak
Activation of guanylate cyclase (GC) A after ischemic stroke is neuroprotective. The aim is to investigate the effect of GC-C activation by uroguanylin (UGN) on ischemic stroke. MCAO was performed on GC-C knock out (GC-C KO), UGN KO mice and their WT littermates. MR images were acquired before and 24h after stroke. Ca2+ response was recorded in astrocytes 48h after MCAO. Systolic (SP), diastolic (DP) and mean arterial blood pressure (MAP) were recorded. GC-C KO develop significantly smaller ischemic lesions. Though they have higher SP, DP and MAP, blood flow or its reduction during MCAO did not differ between KO and WT. Unlike GC-C KO, UGN KO and WT have stronger Ca2+ response to UGN stimulation in peri- ischemic astrocytes and this difference may result in smaller lesions in GC-C KO. Stronger activation was explained when immunohistochemical staining showed GC-C expression in peri-ischemic astrocytes, while under normoxic conditions it is limited to neurons. GC-C activation leads to development of larger lesions. Its expression in peri-ischemic astrocytes causes stronger activation of the Ca2+-dependent signalling pathway which could stimulate the Na+/H+ exchanger causing tissue acidification and neuronal death. 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” ; GAKK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund), “Young researchers' career development project – training of doctoral students” and BRADISCHEMIA (UIP-2017-05-8082) of Croatian Science Foundation funded by European Union’s European Social Fund.

Izvorni jezik
Engleski

Znanstvena područja
Interdisciplinarne prirodne znanosti

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