Suzuki H, Nagashima T, Tamaki N, Yamadori T
Department of Neurosurgery, University of Kobe Medical School, Japan.
Surg Neurol. 1998 Jan;49(1):67-76. doi: 10.1016/s0090-3019(97)98983-7.
It has been reported that cerebral ischemia induces a dissociation between cerebral blood flow and blood-brain barrier glucose transport, but mechanisms of the dissociation are not yet clearly understood. Recent immunohistochemical studies reveal discrepancies of the results between physiologic and immunochemical studies. The purpose of this study was to quantify changes of the blood-brain barrier glucose transporter kinetics following cerebral ischemia by an in situ brain perfusion technique.
Fifty-six adult male Sprague-Dawley rats were divided into control and ischemia groups, and four-vessel occlusion was done as an ischemic insult. To obtain regional capillary permeability surface area products of glucose and regional perfusion fluid flow rates, the perfusion fluid (HCO3-buffered saline) was dually labeled with [14C]-2-Deoxyglucose and [3H]-Diazepam, and the brain was perfused at a constant rate via the external carotid artery. After sampling tissues from three regions (frontal, frontoparietal lobe, and caudoputamen), dual scintillation counting was performed. From the results, we determined kinetic parameters, including Vmax, Km, and Kd as described in the Michaelis-Menten equation, by weighted nonlinear least squares method.
In the ischemia group, the affinity (1/Km) and the maximum glucose transport rate (Vmax) decreased significantly.
The results suggest that severe cerebral ischemia down-regulates the blood-brain barrier glucose transporter kinetics, and the discrepancies between physiologic and immunohistochemical studies may be derived from redistribution of transporters, some deformation of transporters, production of some inhibitors, recruitment of capillaries with different types of transporters, and/or the effect of surrounding glial reaction.
据报道，脑缺血会导致脑血流量与血脑屏障葡萄糖转运之间出现解离，但这种解离的机制尚未完全明确。最近的免疫组织化学研究揭示了生理学和免疫化学研究结果之间的差异。本研究的目的是通过原位脑灌注技术量化脑缺血后血脑屏障葡萄糖转运体动力学的变化。
将56只成年雄性Sprague-Dawley大鼠分为对照组和缺血组，采用四血管闭塞法作为缺血损伤模型。为了获得葡萄糖的区域毛细血管通透性表面积乘积和区域灌注液流速，灌注液（碳酸氢盐缓冲盐水）用[14C]-2-脱氧葡萄糖和[3H]-地西泮进行双重标记，并通过颈外动脉以恒定速率灌注大脑。从三个区域（额叶、额顶叶和尾壳核）采集组织样本后，进行双闪烁计数。根据结果，我们采用加权非线性最小二乘法确定了动力学参数，包括米氏方程中描述的Vmax、Km和Kd。
在缺血组中，亲和力（1/Km）和最大葡萄糖转运速率（Vmax）显著降低。
结果表明，严重脑缺血会下调血脑屏障葡萄糖转运体动力学，生理学和免疫组织化学研究之间的差异可能源于转运体的重新分布、转运体的一些变形、某些抑制剂的产生、具有不同类型转运体的毛细血管的募集和/或周围胶质反应的影响。
