Centre for Prions & Protein Folding Disease, University of Alberta, Edmonton, AB, Canada.
Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.
Methods Mol Biol. 2024;2707:3-22. doi: 10.1007/978-1-0716-3401-1_1.
We describe a straightforward, scalable method for administering traumatic brain injury (TBI) to zebrafish larvae. The pathological outcomes appear generalizable for all TBI types, but perhaps most closely model closed-skull, diffuse lesion (blast injury) neurotrauma. The injury is delivered by dropping a weight onto the plunger of a fluid-filled syringe containing zebrafish larvae. This model is easy to implement, cost-effective, and provides a high-throughput system that induces brain injury in many larvae at once. Unique to vertebrate TBI models, this method can be used to deliver TBI without anesthetic or other metabolic agents. The methods simulate the main aspects of traumatic brain injury in humans, providing a preclinical model to study the consequences of this prevalent injury type and a way to explore early interventions that may ameliorate subsequent neurodegeneration. We also describe a convenient method for executing pressure measurements to calibrate and validate this method. When used in concert with the genetic tools readily available in zebrafish, this model of traumatic brain injury offers opportunities to examine many mechanisms and outcomes induced by traumatic brain injury. For example, genetically encoded fluorescent reporters have been implemented with this system to measure protein misfolding and neural activity via optogenetics.
我们描述了一种简单、可扩展的方法，用于对斑马鱼幼虫进行创伤性脑损伤（TBI）。该方法所导致的病理结果似乎适用于所有 TBI 类型，但可能与闭合性颅脑、弥漫性损伤（冲击伤）的神经创伤最为接近。通过将含有斑马鱼幼虫的充满液体的注射器柱塞上的重物，来实现这种损伤。这种模型易于实施、具有成本效益，并提供了一种高通量系统，可以同时对许多幼虫进行脑损伤。与脊椎动物 TBI 模型不同的是，这种方法可以在不使用麻醉剂或其他代谢剂的情况下进行 TBI。该方法模拟了人类创伤性脑损伤的主要方面，提供了一种临床前模型，用于研究这种常见损伤类型的后果，并探索可能改善随后神经退行性变的早期干预措施。我们还描述了一种方便的压力测量方法，用于校准和验证该方法。当与斑马鱼中易于获得的遗传工具一起使用时，这种创伤性脑损伤模型提供了研究创伤性脑损伤诱导的许多机制和结果的机会。例如，已经使用该系统通过光遗传学实现了遗传编码荧光报告基因，以测量蛋白质错误折叠和神经活动。
