Preconditioning-induced ischemic tolerance stimulates growth factor expression and neurogenesis in adult rat hippocampus
Preconditioning-induced ischemic tolerance stimulates growth factor expression and neurogenesis in adult rat hippocampus
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DOI：
10.1016/j.neuint.2005.07.003
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发表时间：
2005-12-01
影响因子：
4.2
通讯作者：
Vemuganti, R
中科院分区：
文献类型：
--
作者：
Naylor, M;Bowen, KK;Vemuganti, R
预适应（PC）是一种现象，在这种现象中，短暂的缺血损伤诱导对随后的严重缺血损伤的耐受性。近年来的研究表明，成年大鼠脑缺血可上调海马齿状回祖细胞的增殖。我们目前正在评估PC是否也能刺激大鼠脑内祖细胞的增殖。自发性高血压大鼠大脑中动脉短暂闭塞10min诱导PC， 1h诱导局灶性缺血。局灶缺血后祖细胞增殖（定义为BrdU（+）细胞数量）和PC（增加2.7倍，p < 0.05）均显著高于sham。3天前的PC对局灶性缺血诱导的祖细胞增殖既没有抑制作用，也没有增加作用。在缺血组和PC组中，约45%在第1周增殖的祖细胞存活至第3周结束，约21%的祖细胞成熟为NeuN（+）神经元。此外，PC后脑内生长因子IGF1、FGF2、TGF β 1、EGF和PDGF-A mRNA表达显著升高。因此，我们表明，PC的有益作用不仅仅是在缺血后的急性期提供神经保护。PC诱导生长因子表达和神经发生可能是一种积极的适应，可以在缺血损伤的情况下进行有效的修复和可塑性。(c) 2005 Elsevier Ltd版权所有。
Preconditioning (PC) is a phenomenon in which a brief ischemic insult induces tolerance against a subsequent severe ischemic insult. Recent studies showed that cerebral ischemia in adult rat upregulates progenitor cell proliferation in the hippocampal dentate gyrus. We presently evaluated whether PC can also stimulate progenitor cell proliferation in rat brain. Middle cerebral artery was transiently occluded in spontaneously hypertensive rats for 10 min to induce PC and I h to induce focal ischemia. Progenitor cell proliferation (defined as BrdU(+) cell number) significantly increased after focal ischemia (by 3.9-fold; p < 0.05) as well as PC (by 2.7-fold; p < 0.05) compared to sham. PC 3 days prior had neither an inhibitory nor an additive effect on focal ischemia-induced progenitor cell proliferation. In both ischemia and PC groups, similar to 45% of the progenitor cells proliferated in week I survived to the end of week 3 and similar to 21% of those matured into NeuN(+) neurons. Furthermore, cerebral mRNA expression of the growth factors IGF1, FGF2, TGF beta 1, EGF and PDGF-A was significantly elevated after PC. Thus, we show that the beneficial effects of PC extend beyond providing neuroprotection during the acute phase after ischemia. Induction of growth factor expression and neurogenesis by PC might be a positive adaptation for an efficient repair and plasticity in the event of an ischemic insult. (c) 2005 Elsevier Ltd. All rights reserved.