Glucose modulation of spreading depression susceptibility
Glucose modulation of spreading depression susceptibility
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DOI：
10.1038/jcbfm.2012.132
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发表时间：
2013-02-01
影响因子：
6.3
通讯作者：
Ayata, Cenk
中科院分区：
文献类型：
--
作者：
Hoffmann, Ulrike;Sukhotinsky, Irma;Ayata, Cenk
Leao 的传播抑制是一种强烈的传播去极化 (SD) 波，与大量跨膜离子、水和神经递质变化相关。去极化的扩散是偏头痛先兆的基础，并发生在脑损伤中，使其成为潜在的治疗目标。虽然 SD 的易感性可以通过药理学调节，但对于全身生理因素（例如血糖状态）的调节知之甚少。在这项研究中，我们在全面的生理监测下系统地研究了麻醉大鼠血糖对 SD 敏感性的调节作用。高血糖和低血糖由胰岛素或葡萄糖输注引起（血糖分别类似于 40 和 400 mg/dL）。通过直接皮层电刺激引起扩散去极化以确定强度阈值，或通过连续局部应用 KCI 来确定 SD 频率。高血糖提高了电 SD 阈值并降低了 KCI 诱导的 SD 频率，而不会显着影响其他 SD 特性。相比之下，低血糖显着延长了个体和累积SD持续时间，但没有改变电SD阈值或SD频率、幅度或传播速度。这些数据表明，大脑葡萄糖可用性的增加使得组织对 SD 具有抵抗力。脑血流与代谢杂志 (2013) 33, 191-195; doi：10.1038/jcbfm.2012.132； 2012 年 9 月 12 日在线发布
Spreading depression of Leao 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 similar to 40 and 400 mg/dL, respectively). Spreading depolarizations were evoked by direct cortical electrical stimulation to determine the intensity threshold, or by continuous topical KCI application to determine SD frequency. Hyperglycemia elevated the electrical SD threshold and reduced the frequency of KCI-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. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 191-195; doi:10.1038/jcbfm.2012.132; published online 12 September 2012