Effect of sustained-mild and trans ient-severe hyperglycemia on ischemia-induced blood-brain barrier opening
Effect of sustained-mild and trans ient-severe hyperglycemia on ischemia-induced blood-brain barrier opening
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DOI：
10.1038/sj.jcbfm.9600454
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发表时间：
2007-09-01
影响因子：
6.3
通讯作者：
Keep, Richard F.
中科院分区：
文献类型：
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作者：
Ennis, Stenten R.;Keep, Richard F.
本研究的目的是检查在大鼠永久性和短暂性大脑中动脉闭塞期间以及何时发生高血糖的不良影响时，什么水平的高血糖会导致血脑屏障（BBB）破坏。通过测量3 H-菊糖的内流速率常数（Ki）和通过测量脑血浆（C-14-菊糖）和Cr-51-标记的红细胞（RBC）体积来评估脑血管功能。使用不同的葡萄糖方案来产生轻度持续高血糖症（血糖类似于150 mg/dL）或短暂-重度高甘油血症（血糖峰值类似于400 mg/dL）。正如预期的那样，在闭塞时短暂的重度高甘油血症在经历2小时缺血和2小时再灌注的动物中诱导了显著的BBB破坏（与对侧核心相比，渗透性增加25倍）。然而，轻度高血糖模型诱导了类似的破坏。类似地，在永久性闭塞后，两种高血糖模型均增强了破坏，并且它们均产生脑血浆体积的显著减少（类似于50%）。在短暂-重度高血糖缺血2小时的最后5分钟内测量时，表观脑RBC体积也降低。然而，如果Cr-51标记的RBC循环整个2小时，则没有减少，表明RBC捕获。严重高血糖模型中血糖的尖峰用于检查高血糖何时诱导BBB破坏。闭塞后不久的高血压造成严重的破坏。相比之下，90分钟的闭塞后的高血糖引起的破坏很小。这些结果表明，轻度高血糖症对BBB功能有深远的影响，并且非常早期纠正高血糖症对于防止不良反应是必要的。
The purpose of this study was to examine what levels of hyperglycemia cause blood-brain barrier (BBB) disruption during permanent and transient middle cerebral artery occlusion in the rat and when the adverse effects of hyperglycemia occur. Cerebrovascular function was assessed by measuring the influx rate constant (K-i) for 3 H-inulin and by measuring cerebral plasma (C-14-inulin) and Cr-51-labeled red blood cell (RBC) volume. Different glucose protocols were used to produce mild sustained hyperglycemia (blood glucose similar to 150mg/dL) or transient-severe hyperglycernia (with a spike in blood glucose of similar to 400 mg/dL). As expected, transient-severe hyperglycernia at the time of occlusion induced marked BBB disruption in animals undergoing 2h of ischemia with 2h of reperfusion (25-fold increase in permeability compared with the contralateral core). However, the mild hyperglycemia model induced similar disruption. Similarly, after permanent occlusion, both hyperglycemia models enhanced disruption and they both produced marked (similar to 50%) reductions in cerebral plasma volume. Apparent cerebral RBC volume also decreased when measured during the final 5 mins of 2 h of ischemia with transient-severe hyperglycemia. However, there was no decrease if the Cr-51-labeled RBCs were circulated for the whole 2h, indicating RBC trapping. The spike in blood glucose in the severe hyperglycemia model was used to examine when hyperglycemia induced BBB disruption. Hyperglycemia shortly after occlusion caused severe disruption. In contrast, hyperglycemia after 90 mins of occlusion caused little disruption. These results suggest that mild hyperglycemia has a profound effect on BBB function and that very early correction of hyperglycemia is necessary to prevent adverse effects.