Zausinger Stefan, Westermaier Thomas, Plesnila Nikolaus, Steiger Hans-Jakob, Schmid-Elsaesser Robert
Department of Neurosurgery, Ludwig-Maximilians University, Klinikum Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany.
Stroke. 2003 Jun;34(6):1526-32. doi: 10.1161/01.STR.0000070841.31224.29. Epub 2003 May 1.
A combined therapeutic approach has been advocated repeatedly for treatment of focal cerebral ischemia. A clinical example of combined therapy is administration of nimodipine, mannitol, dexamethasone, and barbiturates during temporary occlusion of a cerebral artery in neurovascular surgery. We have recently demonstrated outstanding neuroprotective properties of a combination therapy with magnesium (calcium antagonist and glutamate antagonist), tirilazad (antioxidant), and mild hypothermia (MTH). In this study we compared this treatment strategy with the customary treatment options in a rat model of transient focal cerebral ischemia.
Sprague-Dawley rats (n=120) were subjected to 90 minutes of middle cerebral artery occlusion by an intraluminal filament (n=10 per group). In experiment 1, the customary treatment options (nimodipine, mannitol, dexamethasone, methohexital) were evaluated as monotherapy and in combination. In experiment 2, the customary and the new combination therapy (MTH) were compared. Mild hypothermia (33 degrees C) was maintained for 2 hours. Neurological examinations were performed daily. Infarct size was assessed histologically after 7 days.
In experiment 1, infarct volume was attenuated by 34% at maximum, with mannitol and methohexital being the most effective drugs given as monotherapy. In experiment 2, combined administration of the customary treatment options had no additive effect (infarct volume -36%). Combination therapy with MTH reduced total infarction by 73% and almost completely abolished cortical infarction (-91%). None of the animals of this group had any residual neurological deficit at the end of the observation period (P<0.05 versus all other groups).
The efficacy of drugs (monotherapy or in combination) most commonly used for neuroprotection during neurovascular surgery is limited. The newly proposed combination therapy (magnesium, tirilazad, and mild hypothermia), which is based on pathophysiological considerations, seems to be a promising alternative for neuroprotection in cerebrovascular surgery.
针对局灶性脑缺血的治疗，联合治疗方法已被多次提倡。联合治疗的一个临床实例是在神经血管手术中大脑动脉临时闭塞期间给予尼莫地平、甘露醇、地塞米松和巴比妥类药物。我们最近证明了镁（钙拮抗剂和谷氨酸拮抗剂）、替拉扎特（抗氧化剂）和轻度低温（MTH）联合治疗具有出色的神经保护特性。在本研究中，我们在短暂性局灶性脑缺血大鼠模型中比较了这种治疗策略与传统治疗方案。
将120只Sprague-Dawley大鼠（每组10只）通过腔内细丝进行90分钟的大脑中动脉闭塞。在实验1中，评估了传统治疗方案（尼莫地平、甘露醇、地塞米松、美索比妥）作为单一疗法及联合使用的效果。在实验2中，比较了传统治疗方案与新的联合治疗方案（MTH）。将轻度低温（33摄氏度）维持2小时。每天进行神经学检查。7天后通过组织学评估梗死体积。
在实验1中，梗死体积最大减少了34%，其中甘露醇和美索比妥作为单一疗法时效果最为显著。在实验2中，传统治疗方案联合使用没有附加效果（梗死体积减少36%）。MTH联合治疗使总梗死面积减少了73%，几乎完全消除了皮质梗死（减少91%）。在观察期结束时，该组动物均无任何残留神经功能缺损（与所有其他组相比，P<0.05）。
神经血管手术中最常用于神经保护的药物（单一疗法或联合使用）效果有限。基于病理生理学考虑新提出的联合治疗方案（镁、替拉扎特和轻度低温）似乎是脑血管手术中神经保护的一种有前景的替代方案。
