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在大鼠短暂大脑中动脉闭塞后,人脐带血细胞不能改善感觉运动或认知结果。

Human umbilical cord blood cells do not improve sensorimotor or cognitive outcome following transient middle cerebral artery occlusion in rats.

作者信息

Mäkinen Susanna, Kekarainen Tuija, Nystedt Johanna, Liimatainen Timo, Huhtala Tuulia, Närvänen Ale, Laine Jarmo, Jolkkonen Jukka

机构信息

Department of Neuroscience and Neurology, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland.

出版信息

Brain Res. 2006 Dec 6;1123(1):207-15. doi: 10.1016/j.brainres.2006.09.056. Epub 2006 Oct 30.

Abstract

The present study investigated effects of human umbilical cord blood (HUCB) cells on sensorimotor, cognitive, and histological outcome in rats subjected to transient middle cerebral artery occlusion (MCAO). Halothane anesthetized adult male Wistar rats were subjected to transient MCAO for 2 h. HUCB cells (mononuclear 1-5x10(7) or Lin(-) cells 1-5x10(5)) were administered intravenously after 24 h recovery. The limb-placing test was performed on postoperative days 2, 4, 6, 9, 12, 16, and 20. In addition, beam-walking and cylinder tests were used to assess sensorimotor function at baseline, and on postoperative days 4, 12, and 20. Morris water-maze was used to assess cognitive performance on postoperative days 22-24. Subsequently, rats were perfused for measurement of infarct volumes and detection of HUCB cells by immunohistochemistry (MAB1281). MCAO rats showed a partial spontaneous recovery in sensorimotor function during the follow-up. However, the recovery profile was similar in MCAO controls and in MCAO rats that received HUCB cells. HUCB did not affect impaired water-maze performance of MCAO rats. Only few human nuclei-specific MAB1281-positive cells were detected in the ipsilateral hemisphere in MCAO rats that received HUCB cells. Infarct volumes did not differ between the experimental groups. A group of additional rats were used to further study biodistribution of intravenously given (111)In-oxine-labelled mononuclear HUCB cells in MCAO and sham-operated rats. SPECT imaging data indicated a high tracer uptake in the lung, liver, spleen, and kidney, but not in the brain immediately after administration or 24 h post-administration. The present study suggests that HUCB cells do not improve functional recovery or histological outcome in MCAO rats after systemic administration because of limited migration of cells in the ischemic brain.

摘要

本研究调查了人脐带血细胞(HUCB)对短暂性大脑中动脉闭塞(MCAO)大鼠的感觉运动、认知及组织学结果的影响。用氟烷麻醉成年雄性Wistar大鼠,使其经历2小时的短暂性MCAO。在恢复24小时后静脉注射HUCB细胞(单核细胞1 - 5×10⁷个或Lin⁻细胞1 - 5×10⁵个)。在术后第2、4、6、9、12、16和20天进行肢体放置试验。此外,在基线以及术后第4、12和20天,使用横梁行走试验和圆筒试验来评估感觉运动功能。在术后第22 - 24天,用Morris水迷宫评估认知表现。随后,对大鼠进行灌注以测量梗死体积,并通过免疫组织化学(MAB1281)检测HUCB细胞。在随访期间,MCAO大鼠的感觉运动功能出现部分自发恢复。然而,MCAO对照组和接受HUCB细胞的MCAO大鼠的恢复情况相似。HUCB并未影响MCAO大鼠受损的水迷宫表现。在接受HUCB细胞的MCAO大鼠的同侧半球中,仅检测到少数人细胞核特异性MAB1281阳性细胞。各实验组之间的梗死体积没有差异。另外使用一组大鼠进一步研究静脉注射¹¹¹In - 奥克辛标记的单核HUCB细胞在MCAO大鼠和假手术大鼠中的生物分布。单光子发射计算机断层扫描(SPECT)成像数据表明,给药后即刻及给药后24小时,示踪剂在肺、肝、脾和肾中摄取较高,但在脑中摄取不高。本研究表明,由于缺血脑中细胞迁移有限,全身给药后HUCB细胞并不能改善MCAO大鼠的功能恢复或组织学结果。

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