Folic acid stimulates proliferation of transplanted neural stem cells after focal cerebral ischemia in rats
Folic acid stimulates proliferation of transplanted neural stem cells after focal cerebral ischemia in rats
复制标题
叶酸刺激大鼠局灶性脑缺血后移植神经干细胞的增殖
DOI：
10.1016/j.jnutbio.2013.04.002
复制
发表时间：
2013-11-01
影响因子：
5.6
通讯作者：
Huang, Guowei
中科院分区：
文献类型：
--
作者：
Liu, Huan;Cao, Jiasong;Huang, Guowei
叶酸(FA)可促进大鼠大脑中动脉闭塞(MCAO)后神经干细胞(NSC)的体外增殖，促进海马神经再生。观察补充FA对MCAO大鼠移植的外源性NSCs的影响，以确定FA是否能刺激局灶性脑缺血后NSC的替换。将大鼠随机分为3组：MCAO组、MCAO+外源性NSC移植组(MCAO+NSCs)和MCAO+NSC移植+FA组(MCAO+NSCs+FA)。FA(0.8 mg/kg)或赋形剂在MCAO前28d及以后23d每日灌胃。用超顺磁性氧化铁(SPIO)和溴脱氧尿嘧啶核苷(BrdU)标记神经干细胞，然后移植到缺血区对侧的纹状体内。移植后每隔21天进行一次磁共振成像追踪和荧光免疫组织化学检查，并测量血清叶酸浓度。补充FA可使血清叶酸浓度持续增加400-600%。磁共振图像显示，在MCAO+NSCs+FA大鼠的移植部位和缺血区，SPIO标记的NSCs比MCAO+NSCs大鼠更加丰富。同样，免疫组织化学显示，接受FA的大鼠移植部位和缺血点的Sox-2/BrdU双阳性细胞数量较多。综上所述，局灶性脑缺血后，补充FA可刺激移植的神经干细胞增殖并向缺血区迁移。(C)2013 Elsevier Inc.保留所有权利。
Folic acid (FA) stimulates neural stem cell (NSC) proliferation in vitro and enhances hippocampal neurogenesis in rats after middle cerebral artery occlusion (MCAO). The effect of FA supplementation on exogenous NSCs transplanted in MCAO rats was observed to determine if FA can stimulate NSC replacement after focal cerebral ischemia. Rats were randomly assigned to 3 groups: MCAO; MCAO and exogenous NSC transplantation (MCAO+NSCs); and MCAO, NSC transplantation and FA (MCAO+NSCs +FA). FA (0.8 mg/kg) or vehicle was administered by gavage daily for 28 days before MCAO and 23 days afterward. NSCs were labeled with superparamagnetic iron oxide (SPIO) and bromodeoxyuridine (BrdU) prior to transplantation into the striatum, contralateral to the ischemic zone, at 2 days post-MCAO. Magnetic resonance imaging tracking and fluorescent immunohistochemistry, as well as measurement of serum folate concentration, were performed at intervals up to 21 days after transplantation. FA supplementation caused sustained increases of 400-600% in serum folate concentration. Magnetic resonance images indicated that SPIO-labeled NSCs were more abundant at the transplantation and ischemic brain sites in MCAO+NSCs+FA rats than in MCAO+NSCs rats. Similarly, immunohistochemistry showed that the numbers of Sox-2/BrdU double positive cells at the transplantation and ischemic sites were higher in the rats that received FA. In conclusion, after focal cerebral ischemia, FA supplementation stimulates transplanted NSCs to proliferate and migrate to ischemic sites. (C) 2013 Elsevier Inc. All rights reserved.