Stroke-induced progenitor cell proliferation in adult spontaneously hypertensive rat brain:: effect of exogenous IGF-1 and GDNF
Stroke-induced progenitor cell proliferation in adult spontaneously hypertensive rat brain:: effect of exogenous IGF-1 and GDNF
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DOI：
10.1046/j.1471-4159.2003.02022.x
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发表时间：
2003-11-01
影响因子：
4.7
通讯作者：
Vemuganti, R
中科院分区：
文献类型：
--
作者：
Dempsey, RJ;Sailor, KA;Vemuganti, R
哺乳动物海马齿状回（DG）和侧脑室下区（SVZ）的祖细胞在整个生命过程中产生新的神经元。脑缺血增加基底祖细胞的增殖。本研究对成年自发性高血压大鼠短暂性大脑中动脉闭塞（MCAO）后新生细胞的增殖时间、存活时间和表型进行了评价。与假对照组相比，缺血大鼠DG（4倍，p < 0.05）和SVZ（2倍，p < 0.05）的新增殖细胞数量（BrdU免疫染色定义）均显著增加。DG仅在再灌注第一周增殖增加，在此期间形成的细胞有49%存活至第三周末。而SVZ在MCAO后持续增殖至3周，但形成的细胞存活时间不足1周。在DG和SVZ中，在再灌注第一周结束时，大多数BrdU阳性（BrdU(+)）细胞为未成熟神经元（DCX阳性）。在DG中，28%的细胞在MCAO后第一周形成成熟的神经元（NeuN阳性）。缺血皮质和纹状体可见少量ED-1阳性的BrdU（+）细胞。再灌注1周时，体外灌注IGF-1 （127 +/- 14%, p < 0.05）和GDNF （91 +/- 5%, p < 0.05）显著增加同侧DG中mcao诱导的祖细胞增殖。经生长因子处理的瞬时MCAO大鼠，第一周形成的多个BrdU（+）细胞存活至第三周。
Progenitor cells in the dentate gyrus of hippocampus (DG) and the subventricular zone of lateral ventricles (SVZ) generate new neurons throughout the life of mammals. Cerebral ischemia increases this basal progenitor cell proliferation. The present study evaluated the time frame of proliferation, length of survival and the phenotypes of the new cells formed after transient middle cerebral artery occlusion (MCAO) in adult spontaneously hypertensive rats. Compared to sham controls, ischemic rats showed a significantly higher number of newly proliferated cells (as defined by BrdU immunostaining) in both the DG (by fourfold, p < 0.05) and the SVZ (by twofold, p < 0.05). DG showed increased proliferation only in the first week of reperfusion and 49% of the cells formed in this period survived to the end of third week. Whereas, SVZ showed a continuous proliferation up to 3 weeks after MCAO, but the cells formed survived for less than a week. In both DG and SVZ, at the end of the first week of reperfusion, majority of the BrdU-positive (BrdU(+)) cells were immature neurons (DCX positive). In the DG, 28% of the cells formed in the first week after MCAO mature into neurons (NeuN positive). The ischemic cortex and striatum showed several BrdU(+) cells which were ED-1 positive microglia/macrophages. At 1 week of reperfusion, MCAO-induced progenitor cell proliferation in the ipsilateral DG was significantly increased by i.c.v. infusion of IGF-1 (by 127 +/- 14%, p < 0.05) and GDNF (by 91 +/- 5%, p < 0.05), compared to vehicle. In the growth factor treated rats subjected to transient MCAO, several BrdU(+) cells formed in the first week survived up to the third week.