Sublethal transient global ischemia stimulates migration of neuroblasts and neurogenesis in mice.
Sublethal transient global ischemia stimulates migration of neuroblasts and neurogenesis in mice.
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DOI：
10.1007/s12975-010-0016-6
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发表时间：
2010-09
影响因子：
6.9
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Li Y;Yu SP;Mohamad O;Genetta T;Wei L
越来越多的证据表明，成人大脑受伤后神经元可塑性的潜力。局灶性亚致死缺血预处理事件可以触发神经增殖；轻度全身缺血是否会导致神经发生尚不清楚。本研究调查了亚致死性短暂性整体缺血（TGI）对成人皮质的室下区（SVZ）、齿状回和梗塞周围区域的内源性神经发生和神经母细胞迁移的刺激作用。 129S2/Sv 品系的成年小鼠接受 8 分钟的双侧颈总动脉结扎，然后每天给予 5-溴-2'-脱氧尿苷（BrdU；50 mg/kg，腹膜内），直至再灌注后 1-21 天处死。海马和新皮质 NeuN 阳性细胞中负末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记染色证明，轻度 TGI 在 TGI 后长达 7 天内不会诱导神经元细胞死亡。在 TGI 动物中，BrdU 染色显示神经母细胞的增殖增强，并且它们从 SVZ 迁移到纹状体和新皮质。在胼胝体中，TGI组前2天出现较多BrdU阳性细胞。 7-21 天后，在 TGI 小鼠的纹状体和皮质中观察到 BrdU 阳性细胞数量不断增加。 TGI动物皮质显示促红细胞生成素、促红细胞生成素受体、成纤维细胞生长因子2、血管内皮生长因子和磷酸化Jun N末端激酶的表达增加；再灌注后2至3天表达达到峰值。齿状回、纹状体和皮质中的 BrdU 和 NeuN 双染色表明 TGI 预处理诱导的神经发生增加。 TGI 小鼠皮质中双皮质素 (DCX) 阳性细胞增多，定位于皮质层 II、III 和 V，并且许多细胞对成熟神经元标记 NeuN、神经丝、N-甲基-d-天冬氨酸受体亚基基因 NR1 或 γ-氨基丁酸合成酶谷氨酸脱羧酶 (GAD67) 染色呈阳性。 DCX 阳性细胞的非典型定位以及与成熟神经元标记的共标记表明，除了识别迁移的神经母细胞之外，DCX 也可能是皮质中的应激标记。这表明亚致死 TGI 诱导的再生反应可能有助于缺血预处理的有益效果。
Increasing evidence has shown the potential of neuronal plasticity in adult brain after injury. Neural proliferation can be triggered by a focal sublethal ischemic preconditioning event; whether mild global ischemia could cause neurogenesis has been not clear. The present study investigated stimulating effects of sublethal transient global ischemia (TGI) on endogenous neurogenesis and neuroblast migration in the subventricular zone (SVZ), dentate gyrus, and peri-infarct areas of the adult cortex. Adult mice of 129S2/Sv strain were subjected to 8-min bilateral common carotid artery ligation followed by 5-bromo-2′-deoxyuridine (BrdU; 50 mg/kg, intraperitoneal) administration every day until being sacrificed at 1–21 days after reperfusion. The mild TGI did not induce neuronal cell death for up to 7 days after TGI, as evidenced by negative terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining among NeuN-positive cells in the hippocampus and neocortex. In TGI animals, BrdU staining revealed enhanced proliferation of neuroblasts and their migration track from the SVZ into the striatum and neocortex. In the corpus callosum, there were more BrdU-positive cells in the TGI group in the first 2 days. Increasing numbers of BrdU-positive cells were seen 7–21 days later in the striatum and cortex of TGI mice. The cortex of TGI animals showed increased expression of erythropoietin, erythropoietin receptor, fibroblast growth factor 2, vascular endothelial growth factor, and phosphorylated Jun N-terminal kinase; the expression was peaked 2 to 3 days after reperfusion. BrdU and NeuN double staining in the dentate gyrus, striatum, and cortex implied increased neurogenesis induced by the TGI preconditioning. Doublecortin (DCX)-positive cells increased in the cortex of TGI mice, localized to cortical layers II, III, and V, and many stained positive for the mature neuronal markers NeuN, neurofilament, N-methyl-d-aspartic acid receptor subunit gene NR1, or the gamma-aminobutyric-acid-synthesizing enzyme glutamic acid decarboxylase (GAD67). The atypical localization of DCX-positive cells and the colabeling with mature neuronal markers suggested that, in addition to indentifying migrating neuroblasts, DCX might also be a stress marker in the cortex. It is suggested that the sublethal TGI-induced regenerative responses may contribute to the beneficial effects of ischemic preconditioning.
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影响因子：
8.3
作者：
Majid, A;He, YY;Hsu, CY
通讯作者：
Hsu, CY
影响因子：
2.5
作者：
Brown, JP;Couillard-Després, S;Kuhn, HG
通讯作者：
Kuhn, HG
影响因子：
3.4
作者：
Couillard-Despres, S;Winner, B;Aigner, L
通讯作者：
Aigner, L
影响因子：
3.7
作者：
Bronster, David J
通讯作者：
Bronster, David J
影响因子：
3.5
作者：
Jin, K;Sun, YJ;Greenberg, DA
通讯作者：
Greenberg, DA