Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
J Cereb Blood Flow Metab. 2013 Feb;33(2):191-5. doi: 10.1038/jcbfm.2012.132. Epub 2012 Sep 12.
Spreading depression of Leão is an intense spreading depolarization (SD) wave associated with massive transmembrane ionic, water, and neurotransmitter shifts. Spreading depolarization underlies migraine aura, and occurs in brain injury, making it a potential therapeutic target. While susceptibility to SD can be modulated pharmacologically, much less is known about modulation by systemic physiological factors, such as the glycemic state. In this study, we systematically examined modulation of SD susceptibility by blood glucose in anesthetized rats under full physiological monitoring. Hyperglycemia and hypoglycemia were induced by insulin or dextrose infusion (blood glucose ∼40 and 400 mg/dL, respectively). Spreading depolarizations were evoked by direct cortical electrical stimulation to determine the intensity threshold, or by continuous topical KCl application to determine SD frequency. Hyperglycemia elevated the electrical SD threshold and reduced the frequency of KCl-induced SDs, without significantly affecting other SD properties. In contrast, hypoglycemia significantly prolonged individual and cumulative SD durations, but did not alter the electrical SD threshold, or SD frequency, amplitude or propagation speed. These data show that increased cerebral glucose availability makes the tissue resistant to SD.
莱奥氏扩散性抑制是一种与跨膜离子、水和神经递质大量转移相关的强烈扩散性去极化（SD）波。SD 是偏头痛先兆的基础，也发生在脑损伤中，因此它是一个潜在的治疗靶点。虽然 SD 的易感性可以通过药理学进行调节，但对于系统性生理因素（如血糖状态）的调节知之甚少。在这项研究中，我们在生理监测下的麻醉大鼠中系统地检查了血糖对 SD 易感性的调节作用。通过胰岛素或葡萄糖输注（血糖分别约为 40 和 400mg/dL）诱导高血糖和低血糖。通过直接皮质电刺激诱发扩散性去极化以确定强度阈值，或通过持续局部应用 KCl 来确定 SD 频率。高血糖升高了电 SD 阈值，并降低了 KCl 诱导的 SD 频率，而对其他 SD 特性没有明显影响。相比之下，低血糖显著延长了单个和累积 SD 的持续时间，但没有改变电 SD 阈值、SD 频率、幅度或传播速度。这些数据表明，增加脑葡萄糖的可用性使组织对 SD 具有抵抗力。
