Hepatocyte growth factor improved learning and memory dysfunction of microsphere-embolized rats

Hepatocyte growth factor improved learning and memory dysfunction of microsphere-embolized rats
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DOI:
10.1002/jnr.20263
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发表时间:
2004-11-01
影响因子:
4.2
通讯作者:
Takeo, S
Takeo, S
中科院分区:
医学3区
文献类型:
--
作者:
Date, I;Takagi, N;Takeo, S

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肝细胞生长因子(HGF)是一种促进多种器官再生和保护的有机促生长因子,具有减轻脑缺血所致细胞死亡的作用。然而,HGF对脑缺血后学习记忆功能的影响尚不清楚。我们已经证明,在微球栓塞诱导脑缺血后12-28天,脑室注射人重组HGF(HrHGF)可减少水迷宫获取和保持测试中逃逸潜伏期的延长。HrHGF治疗也减轻了脑缺血后第28天同侧大脑半球存活面积的减少以及脑血管的密度和数量,尤其是直径小于10pm的血管。我们观察到,hrHGF治疗减少了脑缺血后早期TUNEL阳性的脑内皮细胞的数量。这些结果表明,hrHGF通过保护内皮细胞免受损伤,防止持续脑缺血后出现的学习和记忆功能障碍。HGF治疗可能是一种有效的治疗脑血管疾病的策略,包括脑梗塞和血管性痴呆。(C)2004年Wiley-Liss公司
Hepatocyte growth factor (HGF), an organotropic factor for regeneration and protection in various organs, has the ability to attenuate cerebral ischemia-induced cell death. The effect of HGF on learning and memory function after cerebral ischemia, however, remains unknown. We have demonstrated that administration of human recombinant HGF (hrHGF) into the ventricle reduced prolongation of the escape latency in acquisition and retention tests of the water maze task on Days 12-28 after microsphere embolism-induced cerebral ischemia. Treatment with hrHGF also attenuated the decrease in viable area and the density and number of perfused cerebral vessels, particularly those with a diameter smaller than 10 p,m, of the ipsilateral hemisphere on Day 28 after the cerebral ischemia. We observed that treatment with hrHGF reduced the number of TUNEL-positive cerebral endothelial cells at the early stage after the ischemia. These results suggest that hrHGF prevents learning and memory dysfunction seen after sustained cerebral ischemia by protecting against injury to the endothelial cells. HGF treatment may be a potent therapeutic strategy for cerebrovascular diseases, including cerebral infarct and vascular dementia. (C) 2004 Wiley-Liss, Inc.