The effect of hyperglycemia on neurovascular coupling and cerebrovascular patterning in zebrafish.
The effect of hyperglycemia on neurovascular coupling and cerebrovascular patterning in zebrafish.
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DOI：
10.1177/0271678x18810615
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发表时间：
2020-02
期刊：
影响因子：
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通讯作者：
Howarth C
中科院分区：
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作者：
Chhabria K;Plant K;Bandmann O;Wilkinson RN;Martin C;Kugler E;Armitage PA;Santoscoy PL;Cunliffe VT;Huisken J;McGown A;Ramesh T;Chico TJ;Howarth C
神经血管耦合（通过神经血管耦合介导响应神经激活的局部脑血流变化）在包括糖尿病在内的许多疾病中受到损害。目前神经血管耦合的临床前啮齿动物模型依赖于侵入性手术和仪器，但转基因斑马鱼加上成像技术的进步可以实现脑血管解剖、神经激活和脑血管血流动力学的非侵入性量化。因此，我们建立了一种新型非侵入性、非麻醉的神经血管耦合斑马鱼幼虫模型，其中视觉刺激引起视顶盖中的神经元激活，这与顶盖血管中红细胞速度的特定增加有关。我们应用该模型来检查葡萄糖暴露对脑血管模式和神经血管耦合的影响。我们发现斑马鱼长期暴露于葡萄糖会损害顶盖血管模式和神经血管耦合。一氧化氮供体硝普钠挽救了葡萄糖暴露对脑血管模式和功能的所有这些不利影响。我们的结果建立了第一个非哺乳动物神经血管耦合模型，与目前使用啮齿类动物相比，提供了进行更快速的基因修饰和高通量筛选的潜力。此外，利用这种斑马鱼模型，我们揭示了一种改善高血糖对脑血管功能影响的潜在策略。
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.