Belayev L, Busto R, Zhao W, Clemens J A, Ginsberg M D
Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami School of Medicine, Florida 33101, USA.
J Neurosurg. 1997 Oct;87(4):595-601. doi: 10.3171/jns.1997.87.4.0595.
The authors examined the effect of delayed high-concentration albumin therapy on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats. Male Sprague-Dawley rats weighing 270 to 320 g were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion induced by means of a poly-L-lysine-coated intraluminal nylon suture inserted retrograde via the external carotid artery into the internal carotid artery and MCA. The agent (20% human serum albumin [HSA]) or control solution (sodium chloride 0.9%) was administered intravenously at a dosage of 1% of body weight immediately after suture removal following a 2-hour period of MCA occlusion. The animals' neurological status was evaluated during MCA occlusion (at 60 minutes) and daily for 3 days thereafter. The brains were perfusion-fixed, and infarct volumes and brain edema were determined. The HSA significantly improved the neurological score compared with saline at 24 hours after MCA occlusion. The rats treated with HSA also had significantly reduced total infarct volume (by 34%) and brain edema (by 81%) compared with saline-treated rats. There was a strong correlation between hematocrit level and brain edema (p < 0.01), and between total infarct volume or brain edema and neurological score at 24, 48, and 72 hours postinjury (p < 0.0002). These results strongly support the beneficial effect of delayed albumin therapy in transient focal ischemia and indicate its possible usefulness in treating patients with acute ischemic stroke.
作者在大鼠大脑中动脉(MCA)闭塞的高度可重复模型中,研究了延迟高浓度白蛋白治疗对缺血性损伤的影响。体重270至320克的雄性Sprague-Dawley大鼠用氟烷麻醉,通过经颈外动脉逆行插入颈内动脉和MCA的聚-L-赖氨酸包被的腔内尼龙缝线诱导暂时性MCA闭塞120分钟。在MCA闭塞2小时后移除缝线后,立即以1%体重的剂量静脉注射药物(20%人血清白蛋白 [HSA])或对照溶液(0.9%氯化钠)。在MCA闭塞期间(60分钟时)以及此后3天每天评估动物的神经状态。对大脑进行灌注固定,并测定梗死体积和脑水肿情况。与生理盐水相比,MCA闭塞24小时后HSA显著改善了神经评分。与生理盐水处理的大鼠相比,接受HSA治疗的大鼠总梗死体积也显著减少(34%),脑水肿显著减轻(81%)。血细胞比容水平与脑水肿之间存在强相关性(p < 0.01),损伤后24、48和72小时总梗死体积或脑水肿与神经评分之间也存在强相关性(p < 0.0002)。这些结果有力地支持了延迟白蛋白治疗对短暂性局灶性缺血的有益作用,并表明其在治疗急性缺血性中风患者方面可能有用。