Bola R Aaron, Kiyatkin Eugene A
In-Vivo Electrophysiology Unit, Behavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health Baltimore, MD, USA.
Front Physiol. 2016 Feb 15;7:39. doi: 10.3389/fphys.2016.00039. eCollection 2016.
Glucose is the main energetic substrate for the metabolic activity of brain cells and its proper delivery into the extracellular space is essential for maintaining normal neural functions. Under physiological conditions, glucose continuously enters the extracellular space from arterial blood via gradient-dependent facilitated diffusion governed by the GLUT-1 transporters. Due to this gradient-dependent mechanism, glucose levels rise in the brain after consumption of glucose-containing foods and drinks. Glucose entry is also accelerated due to local neuronal activation and neuro-vascular coupling, resulting in transient hyperglycemia to prevent any metabolic deficit. Here, we explored another mechanism that is activated during general anesthesia and results in significant brain hyperglycemia. By using enzyme-based glucose biosensors we demonstrate that glucose levels in the nucleus accumbens (NAc) strongly increase after iv injection of Equthesin, a mixture of chloral hydrate and sodium pentobarbital, which is often used for general anesthesia in rats. By combining electrochemical recordings with brain, muscle, and skin temperature monitoring, we show that the gradual increase in brain glucose occurring during the development of general anesthesia tightly correlate with decreases in brain-muscle temperature differentials, suggesting that this rise in glucose is related to metabolic inhibition. While the decreased consumption of glucose by brain cells could contribute to the development of hyperglycemia, an exceptionally strong positive correlation (r = 0.99) between glucose rise and increases in skin-muscle temperature differentials was also found, suggesting the strong vasodilation of cerebral vessels as the primary mechanism for accelerated entry of glucose into brain tissue. Our present data could explain drastic differences in basal glucose levels found in awake and anesthetized animal preparations. They also suggest that glucose entry into brain tissue could be strongly modulated by pharmacological drugs via drug-induced changes in metabolic activity and the tone of cerebral vessels.
葡萄糖是脑细胞代谢活动的主要能量底物，其正常输送到细胞外空间对于维持正常神经功能至关重要。在生理条件下，葡萄糖通过由GLUT-1转运蛋白介导的梯度依赖性易化扩散，持续从动脉血进入细胞外空间。由于这种梯度依赖性机制，食用含葡萄糖的食物和饮料后，大脑中的葡萄糖水平会升高。由于局部神经元激活和神经血管耦合，葡萄糖进入也会加速，导致短暂性高血糖，以防止任何代谢不足。在此，我们探索了另一种在全身麻醉期间被激活并导致显著脑高血糖的机制。通过使用基于酶的葡萄糖生物传感器，我们证明，静脉注射水合氯醛和戊巴比妥钠的混合物（常用于大鼠全身麻醉的Equthesine）后，伏隔核（NAc）中的葡萄糖水平会大幅升高。通过将电化学记录与大脑、肌肉和皮肤温度监测相结合，我们表明，全身麻醉过程中大脑葡萄糖的逐渐升高与脑-肌肉温度差的降低密切相关，这表明这种葡萄糖升高与代谢抑制有关。虽然脑细胞葡萄糖消耗减少可能导致高血糖的发生，但我们还发现葡萄糖升高与皮肤-肌肉温度差增加之间存在异常强烈的正相关（r = 0.99），这表明脑血管的强烈血管舒张是葡萄糖加速进入脑组织的主要机制。我们目前的数据可以解释清醒和麻醉动物制剂中基础葡萄糖水平的巨大差异。它们还表明，药物可以通过诱导代谢活动和脑血管张力的变化，强烈调节葡萄糖进入脑组织的过程。
