Chhabria, K., Plant, K., Bandmann, O. et al. (11 more authors) (2018) The effect of hyperglycemia on neurovascular coupling and cerebrovascular patterning in zebrafish. Journal of Cerebral Blood Flow and Metabolism, 40 (2). 298 -313. ISSN 0271-678X
Abstract
Neurovascular coupling (through which local cerebral blood flow changes in response to neural activation are mediated) is impaired in many diseases including diabetes. Current preclinical rodent models of neurovascular coupling rely on invasive surgery and instrumentation, but transgenic zebrafish coupled with advances in imaging techniques allow non-invasive quantification of cerebrovascular anatomy, neural activation, and cerebral vessel haemodynamics. We therefore established a novel non-invasive, non-anaesthetised zebrafish larval model of neurovascular coupling, in which visual stimulus evokes neuronal activation in the optic tectum that is associated with a specific increase in red blood cell speed in tectal blood vessels.
We applied this model to the examination of the effect of glucose exposure on cerebrovascular patterning and neurovascular coupling. We found that chronic exposure of zebrafish to glucose impaired tectal blood vessel patterning and neurovascular coupling. The nitric oxide donor sodium nitroprusside rescued all these adverse effects of glucose exposure on cerebrovascular patterning and function. Our results establish the first non-mammalian model of neurovascular coupling, offering the potential to perform more rapid genetic modifications and high throughput screening than is currently possible using rodents. Furthermore, using this zebrafish model we reveal a potential strategy to ameliorate the effects of hyperglycemia on cerebrovascular function.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 The Authors. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
Keywords: | Cerebrovascular patterning; diabetes; neurovascular coupling; nitric oxide; zebrafish |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Psychology (Sheffield) |
Funding Information: | Funder Grant number WELLCOME TRUST (THE) 105586/Z/14/Z NATIONAL CENTRE FOR THE REPLACEMENT, REFINEMENT AND REDUCTION OF ANIMALS IN RESEARCH NC/P001173/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Oct 2018 12:10 |
Last Modified: | 10 May 2024 14:54 |
Status: | Published |
Publisher: | SAGE Publications |
Refereed: | Yes |
Identification Number: | 10.1177/0271678X18810615 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:136605 |