甘露醇促进人脐血CD34+细胞通过血脑屏障静脉迁移至高血压脑梗死大鼠脑组织

背景：单纯脐血细胞经静脉移植治疗脑梗死疗效有限，移植细胞经血脑屏障迁入脑内数量不足为重要原因之一。目的：观察血脑屏障开放剂甘露醇对人脐血CD34⁺细胞经静脉移植治疗高血压大鼠脑梗死疗效的影响。方法：分离人脐血CD34⁺细胞，脂质体方法转染pEGFPF质粒，制备pEGFP-CD34⁺细胞；45只雄性SD大鼠经线栓法建立大脑中动脉栓塞模型，造模后24 h随机分为3组：实验组注射1×10⁶ GFP-CD34⁺细胞，继之注射20%甘露醇2 g/kg；阳性对照组注射1×10⁶ GFP-CD34⁺细胞；空白对照组注射等量生理盐水。结果与结论：①荧光显微镜下实验组每张切片脑组织GFP标记阳性的绿色荧光细胞计数平均值显著多于阳性对照组。②移植后第7天治疗组与其他各组神经功能损害评分差异无显著性意义；移植后28 d，各组神经功能均有不同程度恢复，实验组神经功能恢复明显优于阳性对照组和空白对照组(P < 0.05)。③实验组与其他两组相比，大鼠脑梗死体积均显著减少。④实验组脑组织匀浆胶质细胞源性神经营养因子水平较阳性对照组、空白对照组明显增高。提示血脑屏障开放剂甘露醇促进静脉移植CD34⁺细胞通过血脑屏障迁入至脑组织，并增强静脉移植CD34⁺细胞治疗脑梗死的疗效。

Mannitol improves the efficacy of intravenous transplantation of human umbilical cord blood CD34+ cells for cerebral infarction in hypertensive rats

BACKGROUND: Intravenous transplantation of human umbilical cord blood cells (HUCBCs) in treatment of cerebral infarction is limited. Only a small fraction of the grafted cells appears to survive at the damaged brain and the behavioral recovery is only partial.OBJECTIVE:To evaluate the ability of Mannitol, a blood brain barrier (BBB) permeabilizer, to enhance neuroprotective effects of intravenously administered HUCBCs for cerebral infarction in spontaneous hypertensive rats.METHODS:CD34⁺ cells isolated from HUCB were transfected by GFP plasmid with liposome method. Forty-five adult male spontaneous hypertensive rats with middle cerebral artery occlusion were randomly divided into three groups at 24 hours after modeling, each of 15: Experimental group, GFP-CD34⁺ cells (1×10⁶) and 20% Mannitol (2 g/kg) were administrated intravenously at 24 hours after modeling; Positive control group, GFP-CD34⁺ cells (1×10⁶) were only injected intravenously at same time; Blank control group, normal saline was injected at same time. RESULTS AND CONCLUSION:①The number of GFP positive cells in cerebral tissues in the experimental group was increased significantly compared to the positive control group. ②No significant difference was found in the neurologic function scores at day 7 after transplantation among the three groups; but at day 28 after transplantation, the neurologic function in the experimental group was improved significantly compared with the positive or blank control group (P < 0.05). ③The cerebral infarct volume in the experimental group was significantly decreased compared with the positive or blank control group. ④The glial cell line-derived neurotrophic factor level in cerebral tissue in the experimental group was significantly increased compared with the positive and blank control groups. The results suggested that Mannitol enhanced CD34⁺ cells to migrate into ischemic-injured cerebral tissues, and to improve the efficacy of CD34⁺ cells delivered intravenously for cerebral infarction in spontaneous hypertensive rats.