ZFIN ID: ZDB-PUB-181107-4
The effect of hyperglycemia on neurovascular coupling and cerebrovascular patterning in zebrafish
Chhabria, K., Plant, K., Bandmann, O., Wilkinson, R.N., Martin, C., Kugler, E., Armitage, P.A., Santoscoy, P.L., Cunliffe, V.T., Huisken, J., McGown, A., Ramesh, T., Chico, T.J., Howarth, C.
Date: 2018
Source: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism   40(2): 298-313 (Journal)
Registered Authors: Bandmann, Oliver, Chico, Tim J., Cunliffe, Vincent, Huisken, Jan, McGown, Alexander, Wilkinson, Robert
Keywords: Cerebrovascular patterning, diabetes, neurovascular coupling, nitric oxide, zebrafish
MeSH Terms:
  • Action Potentials
  • Animals
  • Brain*/blood supply
  • Brain*/pathology
  • Brain*/physiopathology
  • Cerebral Arteries/pathology
  • Cerebral Arteries/physiopathology
  • Cerebral Veins/pathology
  • Cerebral Veins/physiopathology
  • Cerebrovascular Circulation*
  • Hyperglycemia*/blood
  • Hyperglycemia*/pathology
  • Hyperglycemia*/physiopathology
  • Neovascularization, Pathologic*/pathology
  • Neovascularization, Pathologic*/physiopathology
  • Neurovascular Coupling*
  • Zebrafish
PubMed: 30398083 Full text @ J. Cereb. Blood Flow Metab.
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.