Pregled bibliografske jedinice broj: 1257773
Effects of guanylate cyclase-C activation on ischemic stroke
Effects of guanylate cyclase-C activation on ischemic stroke // 3rd Regional Congress of Physiological Societies and the 5th Congress of Croatian Physiological Society
NP Plitvička jezera, Hrvatska, 2022. str. 80-80 (poster, međunarodna recenzija, sažetak, znanstveni)
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Naslov
Effects of guanylate cyclase-C activation 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
3rd Regional Congress of Physiological Societies and the 5th Congress of Croatian Physiological Society
Mjesto i datum
NP Plitvička jezera, Hrvatska, 22.09.2022. - 24.09.2022
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 the world. Guanylate cyclase (GC) A activation after ischemic stroke is neuroprotective. 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) were recorded with a non-invasive tail-cuff method. Immunohistochemical staining and in situ hybridization were used to confirm GC-C expression in neurons and astrocytes before any after stroke induction. RESULTS: GC-C KO mice develop 35% smaller ischemic lesions compared with their WT littermates. Although higher SP, DP and MAP were recorded in GC-C KO animals when compared with WT mice, blood flow or the reduction of blood flow during MCAO did not differ between those test groups. A stronger Ca2+ response to UGN stimulation was recorded in in cortical peri-ischemic astrocytes of UGN KO and WT mice but 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 difference in Ca2+ response could be explained by the shift in GC-C expression that occurs after stroke – under normoxic conditions GC-C is expressed only in neurons, but after ischemic injury GC-C becomes strongly expressed in peri-ischemic astrocytes and is rarely found in neurons. 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 likely stimulates the Na+/H+ exchanger, leading to 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
Projekti:
--KK.01.1.1.01.0007 - Znanstveni centar izvrnosti - Eksperimentalna i klinička istraživanja hipoksijsko-ishemijskog oštećenja mozga u perinatalnoj i odrasloj dobi (ZCI - NEURO) (Judaš, Miloš) ( CroRIS)
Ustanove:
Medicinski fakultet, Zagreb
Profili:
Martina Ratko
(autor)
Aleksandra Sinđić
(autor)
Siniša Škokić
(autor)
Nikola Habek
(autor)
Anja Barić
(autor)