Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotection in stroke
Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotection in stroke
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DOI：
10.1161/01.str.0000141680.49960.d7
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发表时间：
2004-10-01
期刊：
影响因子：
8.3
通讯作者：
Sanberg, PR
中科院分区：
文献类型：
--
作者：
Borlongan, CV;Hadman, M;Sanberg, PR
背景和目的：迄今为止，干细胞移植物介导的神经保护作用等同于移植物存活和脑内神经营养因子的分泌。在这里，我们研究是否神经保护系统提供的人脐带血（HUCB）细胞依赖于他们进入中枢神经系统的啮齿动物模型急性stroke. Methods成年雄性Sprague-Dawley大鼠进行右大脑中动脉闭塞60分钟。在1小时闭塞期间，将动物随机分配至以下处理之一：静脉内注射HUCB（亚治疗剂量为10穆尔中200000个细胞）与血脑屏障（BBB）透化剂（4 ℃下1.1 mol/L甘露醇）或载体，单独静脉内载体，或单独静脉内甘露醇。在中风后第3天进行行为学测试，使用升高的身体摆动试验和被动回避试验，之后，动物被安乐死用于：（1）HUCB的免疫组织化学检查，其是用绿色荧光蛋白慢病毒标记的;和（3）酶联免疫吸附试验的纹状体region.Results-We没有检测到静脉注射低剂量的HUCB细胞在脑卒中后第3天的动物，即使当细胞与血脑屏障透化剂（甘露醇）。然而，HUCB-甘露醇治疗显着增加脑神经营养因子的水平，这与减少脑梗死和改善行为functions. Conclusions，我们的数据表明，移植细胞的中枢神经系统的可用性是不是急性神经保护的先决条件，这些细胞分泌的治疗分子可以跨越血脑屏障。
Background and Purpose-To date, stem cell graft-mediated neuroprotection is equated with graft survival and secretion of neurotrophic factors in the brain. Here, we examined whether neuroprotection by systemically delivered human umbilical cord blood (HUCB) cells was dependent on their entry into the central nervous system in a rodent model of acute stroke.Methods-Adult male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion for 60 minutes. During the 1-hour occlusion, animals were randomly assigned to 1 of the following treatments: intravenous injection of HUCB (a subtherapeutic dose of 200 000 cells in 10 muL) with blood-brain barrier (BBB) permeabilizer (1.1 mol/L mannitol at 4 C) or vehicle, intravenous vehicle alone, or intravenous mannitol alone. Behavioral tests, using elevated body swing test and passive avoidance test, were conducted at day 3 poststroke, and thereafter, animals were euthanized for: ( 1) immunohistochemical examination of HUCB, which were lentivirally labeled with green fluorescent protein; ( 2) cerebral infarction analysis using 2,3,5-triphenyl-tetrazolium chloride; and ( 3) enzyme-linked immunosorbent assay of trophic factors within the striatal region.Results-We did not detect intravenously administered low dose of HUCB cells in the brains of animals at day 3 after stroke even when cells were coinfused with a BBB permeabilizer (mannitol). However, HUCB-mannitol treatment significantly increased brain levels of neurotrophic factors, which correlated positively with reduced cerebral infarcts and improved behavioral functions.Conclusions-Our data show that central nervous system availability of grafted cells is not a prerequisite for acute neuroprotection provided that therapeutic molecules secreted by these cells could cross the BBB.