Department of Pediatrics, Division of Pediatric Neurosciences, University of Alberta, 11405 87 Avenue, Edmonton, Alberta T6G 1C9, Canada.
Department of Chemical and Materials Engineering, University of Alberta, 11487 89 Avenue, Edmonton, Alberta T6G 2M7, Canada.
J Neurosci Methods. 2023 Apr 15;390:109838. doi: 10.1016/j.jneumeth.2023.109838. Epub 2023 Mar 17.
The interruption of oxygen and blood supply to the newborn brain around the time of birth is a risk factor for hypoxic-ischemic encephalopathy and may lead to infant mortality or lifelong neurological impairments. Currently, therapeutic hypothermia, the cooling of the infant's head or entire body, is the only treatment to curb the extent of brain damage.
In this study, we designed a focal brain cooling device that circulates cooled water at a steady state temperature of 19 ± 1 °C through a coil of tubing fitted onto the neonatal rat's head. We tested its ability to selectively decrease brain temperature and offer neuroprotection in a neonatal rat model of hypoxic-ischemic brain injury.
Our method cooled the brain to 30-33 °C in conscious pups, while keeping the core body temperature approximately 3.2 °C warmer. Furthermore, the application of the cooling device to the neonatal rat model demonstrated a reduction in brain volume loss compared to pups maintained at normothermia and achieved a level of brain tissue protection the same as that of whole-body cooling.
Prevailing methods of selective brain hypothermia are designed for adult animal models rather than for immature animals such as the rat as a conventional model of developmental brain pathology. Contrary to existing methods, our method of cooling does not require surgical manipulation or anaesthesia.
Our simple, economical, and effective method of selective brain cooling is a useful tool for rodent studies in neonatal brain injury and adaptive therapeutic interventions.
新生儿出生时，大脑的氧气和血液供应中断是缺氧缺血性脑病的一个风险因素，可能导致婴儿死亡或终身神经损伤。目前，治疗性低温，即冷却婴儿的头部或整个身体，是遏制脑损伤程度的唯一治疗方法。
在这项研究中，我们设计了一种局灶性脑冷却装置，通过套在新生大鼠头部的盘管以稳定的 19±1°C 温度循环冷却用水。我们测试了其在缺氧缺血性脑损伤新生大鼠模型中选择性降低脑温并提供神经保护的能力。
我们的方法将大脑冷却到清醒幼崽的 30-33°C，同时使核心体温升高约 3.2°C。此外，与保持正常体温的幼崽相比，冷却装置在新生大鼠模型中的应用减少了脑体积损失，并达到了与全身冷却相同的脑组织保护水平。
现有的选择性脑低温方法是为成年动物模型设计的，而不是为不成熟的动物设计的，如大鼠作为发育性脑病理学的常规模型。与现有的方法不同，我们的冷却方法不需要手术操作或麻醉。
我们简单、经济、有效的选择性脑冷却方法是研究新生儿脑损伤和适应性治疗干预的啮齿动物研究的有用工具。
