Shimauchi M, Yamamoto Y L
Cone Neurosurgical Research Laboratory, McGill University, Montreal, Quebec, Canada.
Stroke. 1992 Dec;23(12):1805-10; discussion 1810-1. doi: 10.1161/01.str.23.12.1805.
The ischemic edema associated with blood-brain barrier permeability changes and the excess production of free radicals are serious complications in prolonged cerebral ischemia. We examined the efficacy of transvenous perfusion of the brain, starting treatment 5 hours after occlusion of the middle cerebral artery for a period of 2 hours in rats with the combined agents mannitol (10 ml/2 hr) and dexamethasone (1 mg/2 hr) to counter edema and verapamil (0.05 mg/kg/2 hr) for vasodilation.
In experiment 1, blood-brain barrier permeability changes were examined in five groups with six rats each: group C rats underwent 7 hours of middle cerebral artery occlusion with no treatment; group V, treatment with verapamil alone; group VD, treatment with verapamil and dexamethasone; group VM, treatment with verapamil and mannitol; and group VDM, treatment with verapamil, dexamethasone, and mannitol. In experiment 2, we examined local cerebral blood flow, ischemic tissue damage volume, and water content of cerebral hemispheres in two groups of 16 rats each subjected to the same treatment as groups C and VDM rats in experiment 1.
There was a significant reduction of blood-brain barrier permeability changes in the ischemic cortex of rats in group VDM compared with rats in the other groups. In the group undergoing transvenous perfusion of the brain with the three combined agents, there was a significant improvement of cerebral blood flow (39-58%, p < 0.05) in the ischemic cortex and reduction of ischemic cerebral damage volume (22%, p < 0.01) and water content of the ischemic hemisphere (p < 0.05) compared with the control group.
The therapeutic approach using combined agents is effective treatment when initiated within 5 hours of focal cerebral ischemia in rats.
与血脑屏障通透性改变相关的缺血性水肿以及自由基的过度产生是长时间脑缺血的严重并发症。我们研究了经静脉灌注脑的疗效，在大鼠大脑中动脉闭塞5小时后开始治疗，持续2小时，联合使用甘露醇（10毫升/2小时）和地塞米松（1毫克/2小时）以对抗水肿，维拉帕米（0.05毫克/千克/2小时）用于血管舒张。
在实验1中，对五组每组6只大鼠检测血脑屏障通透性变化：C组大鼠经历7小时大脑中动脉闭塞且未治疗；V组，仅用维拉帕米治疗；VD组，用维拉帕米和地塞米松治疗；VM组，用维拉帕米和甘露醇治疗；VDM组，用维拉帕米、地塞米松和甘露醇治疗。在实验2中，我们检测了两组每组16只大鼠的局部脑血流量、缺血组织损伤体积和脑半球含水量，这两组大鼠接受与实验1中C组和VDM组大鼠相同的治疗。
与其他组大鼠相比，VDM组大鼠缺血皮质的血脑屏障通透性变化显著降低。在接受三种联合药物经静脉灌注脑的组中，与对照组相比，缺血皮质的脑血流量显著改善（39% - 58%，p < 0.05），缺血性脑损伤体积减少（22%，p < 0.01），缺血半球含水量降低（p < 0.05）。
在大鼠局灶性脑缺血5小时内开始使用联合药物的治疗方法是有效的治疗手段。
