Naslov
Effects of uroguanylin's GC-C/cGMP 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
10th Internationak Conference on cGMP

Mjesto i datum
Augsburg, Njemačka, 17.06.2022. - 19.06.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

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

Sažetak
INTRODUCTION: Stroke is one of the leading causes of mortality and disability in industrialized countries. Guanylate cyclase (GC) A activation after ischemic stroke is neuroprotective1. The aim of this study is to investigate what effect GC-C activation by uroguanylin (UGN) has on ischemic stroke. MATERIALS AND METHODS: Middle cerebral artery occlusion (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 induction. Ca2+ response was recorded in astrocytes of peri-ischemic and contralateral cortices 48h after MCAO. Systolic (SP), diastolic (DP) and mean arterial blood pressure (MAP), heart rate, tail blood volume and flow were recorded with a non-invasive tail-cuff method. RESULTS: Animals lacking GC-C develop significantly smaller ischemic lesions compared to their WT littermates. Though GC-C KO mice have higher SP, DP and MAP, blood flow or the reduction of blood flow during MCAO did not differ between KO and WT animals. UGN KO and WT mice have a stronger Ca2+ response to UGN stimulation in cortical peri-ischemic astrocytes compared to the healthy hemisphere while this stronger activation is absent in GC-C KO mice. The observed difference in response may result in smaller ischemic lesions observed in GC-C KO mice. This was explained when immunohistochemical staining showed GC-C expression in peri-ischemic astrocytes, while under normoxic conditions GC-C expression is present only in neurons2. CONCLUSION: Contrary to GC-A, GC-C activation is not neuroprotective but instead leads to the development of larger ischemic lesions. Its expression in peri-ischemic astrocytes causes a 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” ; GA KK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund). The work of doctoral student Anja Barić has been fully supported by the “Young researchers' career development project – training of doctoral students” and project BRADISCHEMIA (UIP-2017-05- 8082) of the Croatian Science Foundation funded by the European Union from the European Social Fund.

Izvorni jezik
Engleski

Znanstvena područja
Interdisciplinarne prirodne znanosti

POVEZANOST RADA