期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 40, 期 2, 页码 298-313出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X18810615
关键词
Cerebrovascular patterning; diabetes; neurovascular coupling; nitric oxide; zebrafish
资金
- MRC [MR/R011354/1] Funding Source: UKRI
- Wellcome Trust [105586/Z/14/Z] Funding Source: Wellcome Trust
- British Heart Foundation [PG/13/2/29902, PG/15/17/31332, IG/15/1/31328] Funding Source: Medline
- Medical Research Council [MR/R011354/1] Funding Source: Medline
- National Centre for the Replacement, Refinement and Reduction of Animals in Research [NC/P001173/1] Funding Source: Medline
- Wellcome Trust [105586/Z/14/Z] Funding Source: Medline
- Motor Neurone Disease Association [RAMESH/APR17/854-791] Funding Source: Medline
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.
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