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  Cerebrovascular G i Proteins Protect Against Brain Hypoperfusion and Collateral Failure in Cerebral Ischemia

Castaneda-Vega, S., Beer-Hammer, S., Leiss, V., Napieczyńska, H., Vuozzo, M., Schmid, A., et al. (2022). Cerebrovascular G i Proteins Protect Against Brain Hypoperfusion and Collateral Failure in Cerebral Ischemia. Molecular Imaging & Biology, Epub ahead. doi:10.1007/s11307-022-01764-8.

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Castaneda-Vega, S, Author
Beer-Hammer, S, Author
Leiss, V, Author
Napieczyńska, H, Author
Vuozzo, M, Author
Schmid, AM, Author
Zeng, H1, Author           
He, Y1, Author           
Kohlhofer, U, Author
Gonzalez-Menendez, I, Author
Quintanilla-Martinez, L, Author
Hempel, J-M, Author
Gollasch, M, Author
Yu, X, Author           
Pichler, BJ, Author
Nürnberg, B, Author
Affiliations:
1Research Group Translational Neuroimaging and Neural Control, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_2528695              

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 Abstract: Cerebral hypoperfusion and vascular dysfunction are closely related to common risk factors for ischemic stroke such as hypertension, dyslipidemia, diabetes, and smoking. The role of inhibitory G protein-dependent receptor (GiPCR) signaling in regulating cerebrovascular functions remains largely elusive. We examined the importance of GiPCR signaling in cerebral blood flow (CBF) and its stability after sudden interruption using various in vivo high-resolution magnetic resonance imaging techniques. To this end, we induced a functional knockout of GiPCR signaling in the brain vasculature by injection of pertussis toxin (PTX). Our results show that PTX induced global brain hypoperfusion and microvascular collapse. When PTX-pretreated animals underwent transient unilateral occlusion of one common carotid artery, CBF was disrupted in the ipsilateral hemisphere resulting in the collapse of the cortically penetrating microvessels. In addition, pronounced stroke features in the affected brain regions appeared in both MRI and histological examination. Our findings suggest an impact of cerebrovascular GiPCR signaling in the maintenance of CBF, which may be useful for novel harmacotherapeutic approaches to prevent and treat cerebrovascular dysfunction and stroke.

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 Dates: 2022-09
 Publication Status: Published online
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 Identifiers: DOI: 10.1007/s11307-022-01764-8
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Title: Molecular Imaging & Biology
Source Genre: Journal
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Publ. Info: New York, NY : Springer
Pages: - Volume / Issue: Epub ahead Sequence Number: - Start / End Page: - Identifier: ISSN: 1860-2002
CoNE: https://pure.mpg.de/cone/journals/resource/18602002