Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
University Center of Competence Sleep & Health Zurich (CRPP), University of Zurich, Zurich, Switzerland.
J Sleep Res. 2022 Dec;31(6):e13615. doi: 10.1111/jsr.13615. Epub 2022 Apr 26.
Modulation of slow-wave activity, either via pharmacological sleep induction by administering sodium oxybate or sleep restriction followed by a strong dissipation of sleep pressure, has been associated with preserved posttraumatic cognition and reduced diffuse axonal injury in traumatic brain injury rats. Although these classical strategies provided promising preclinical results, they lacked the specificity and/or translatability needed to move forward into clinical applications. Therefore, we recently developed and implemented a rodent auditory stimulation method that is a scalable, less invasive and clinically meaningful approach to modulate slow-wave activity by targeting a particular phase of slow waves. Here, we assessed the feasibility of down-phase targeted auditory stimulation of slow waves and evaluated its comparative modulatory strength in relation to the previously employed slow-wave activity modulators in our rat model of traumatic brain injury. Our results indicate that, in spite of effectively reducing slow-wave activity in both healthy and traumatic brain injury rats via down-phase targeted stimulation, this method was not sufficiently strong to counteract the boost in slow-wave activity associated with classical modulators, nor to alter concomitant posttraumatic outcomes. Therefore, the usefulness and effectiveness of auditory stimulation as potential standalone therapeutic strategy in the context of traumatic brain injury warrants further exploration.
通过给予羟丁酸钠诱导药物睡眠或睡眠限制后强烈消除睡眠压力来调节慢波活动，已被证明与创伤性脑损伤大鼠的创伤后认知功能保留和弥漫性轴索损伤减少有关。尽管这些经典策略提供了有前景的临床前结果，但它们缺乏特异性和/或可转化性，无法推进到临床应用。因此，我们最近开发并实施了一种啮齿动物听觉刺激方法，这是一种可扩展的、较少侵入性的、具有临床意义的方法，可以通过靶向慢波的特定相位来调节慢波活动。在这里，我们评估了慢波下相靶向听觉刺激的可行性，并评估了其相对于我们在创伤性脑损伤大鼠模型中先前使用的慢波活动调节剂的比较调节强度。我们的结果表明，尽管通过下相靶向刺激有效地降低了健康和创伤性脑损伤大鼠的慢波活动，但这种方法的强度不足以抵消与经典调节剂相关的慢波活动的增加，也无法改变伴随的创伤后结果。因此，听觉刺激作为创伤性脑损伤背景下潜在的独立治疗策略的有用性和有效性需要进一步探索。
