Role of uroguanylin's signalling pathway in the development of ischaemic stroke

Scientific paper - Original scientific paper

• Author: Martina Ratko
• Author: Nikola Habek
• Author: Marina Dobrivojević Radmilović
• Author: Siniša Škokić
• Author: Helena Justić
• Author: Anja Barić
• Author: Aleksandra Dugandžić
• Author's institution: University of Zagreb; School of Medicine; (Croatian Institiute for Brain Research)
• Author's institution: University of Zagreb; School of Medicine; (Department of Physiology and Immunology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Human Physiology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience

Abstract (english)

Stroke is one of the leading causes of mortality and disability worldwide. By affecting bradykinin function, activation of guanylate cyclase (GC)-A has been shown to have a neuroprotective effect after ischaemic stroke, whereas the same has not been confirmed for GC-B; therefore, we aimed to determine the possible role of GC-C and its agonist, uroguanylin (UGN), in the development of stroke. In this study, middle cerebral artery occlusion (MCAO) was performed on wild-type (WT), GC-C KO and UGN KO mice. MR images were acquired before and 24 h after MCAO. On brain slices 48 h after MCAO, the Ca2+ response to UGN stimulation was recorded. Our results showed that the absence of GC-C in GC-C KO mice resulted in the development of smaller ischaemic lesions compared with WT littermates, which is an opposite effect compared with the effects of GC-A agonists on brain lesions. WT and UGN KO animals showed a stronger Ca2+ response upon UGN stimulation in astrocytes of the peri-ischaemic cerebral cortex compared with the same cortical region of the unaffected contralateral hemisphere. This stronger activation was not observed in GC-C KO animals, which may be the reason for smaller lesion development in GC-C KO mice. The reason why GC-C might affect Ca2+ signalling in peri-ischaemic astrocytes is that GC-C is expressed in these cells after MCAO, whereas under normoxic conditions, it is expressed mainly in cortical neurons. Stronger activation of the Ca2+ -dependent signalling pathway could lead to the stronger activation of the Na+ /H+ exchanger, tissue acidification and neuronal death.

• Keywords (english): Animals; Brain Ischemia; Guanylate Cyclase; Ischemic Stroke; Mice; Mice, Knockout; Natriuretic Peptides; Receptors, Peptide / metabolism; Stroke
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: European Journal of Neuroscience
• Numbering: vol. 56, no. 1, pp. 3720-3737
• p-ISSN: 0953-816X
• e-ISSN: 1460-9568
• DOI: https://doi.org/10.1111/ejn.15674
• URN:NBN: urn:nbn:hr:105:150363
• Publication: 2022-07
• Document URL: https://onlinelibrary.wiley.com/doi/10.1111/ejn.15674
• Type of resource: Text
• Access conditions: Open access
• Created on: 2022-12-09 12:20:09