Kuge Atsushi, Takemura Sunao, Kokubo Yasuaki, Sato Shinya, Goto Kaoru, Kayama Takamasa
Department of Neurosurgery, Faculty of Medicine, Yamagata University, Yamagata, Japan.
Neurol Res. 2009 Nov;31(9):969-76. doi: 10.1179/174313209X383312. Epub 2009 Jan 9.
In the adult mammalian brain, it is considered that neurogenesis persists in limited regions such as the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ) of the lateral ventricle. On the other hand, neurogenesis in the cortex after cerebral ischemia and its role in post-stroke recovery have not been clarified yet. In this study, we investigated neurogenesis in the cortex and the spatiotemporal profile of neural progenitors in SVZ and DG of rats subjected to transient focal cerebral ischemia.
Male Sprague-Dawley rats (270-300 g) were subjected to 60 minute middle cerebral artery occlusion. Proliferating cells were labeled by the cumulative administration of BrdU 1, 2, 3, 4, 6 and 8 weeks after ischemia induction (at weeks 1-4, 6 and 8). Double labeling was also performed with antibodies against BrdU and NeuN.
BrdU-positive cells proliferated in DG and SVZ of the bilateral hemispheres, and their proliferation peaked at week 3 in SVZ and at week 4 in DG. In the peri-infarct zone of cerebral cortex, BrdU-positive cells co-expressed NeuN from weeks 3 to 8.
Neurogenesis was observed in the cerebral cortex and proliferation of neural progenitors occurred in SVZ and DG of rats subjected to transient focal cerebral ischemia. Our data might indicate that endogenous dormant neural stem cells residing in the cortex were activated by ischemic insult to induce the proliferation of neural progenitors and differentiation into mature neurons.
在成年哺乳动物大脑中,人们认为神经发生仅在有限区域持续存在,如海马齿状回(DG)和侧脑室室下区(SVZ)。另一方面,脑缺血后皮质中的神经发生及其在中风后恢复中的作用尚未阐明。在本研究中,我们调查了短暂性局灶性脑缺血大鼠皮质中的神经发生以及SVZ和DG中神经祖细胞的时空分布情况。
雄性Sprague-Dawley大鼠(270 - 300 g)接受60分钟的大脑中动脉闭塞。在缺血诱导后1、2、3、4、6和8周(第1 - 4周、6周和8周)通过累积给予BrdU标记增殖细胞。还使用抗BrdU和NeuN抗体进行双重标记。
BrdU阳性细胞在双侧半球的DG和SVZ中增殖,其增殖在SVZ于第3周达到峰值,在DG于第4周达到峰值。在大脑皮质梗死周围区域,BrdU阳性细胞在第3至8周共表达NeuN。
在短暂性局灶性脑缺血大鼠的大脑皮质中观察到神经发生,并且神经祖细胞在SVZ和DG中增殖。我们的数据可能表明,存在于皮质中的内源性静止神经干细胞被缺血损伤激活,从而诱导神经祖细胞增殖并分化为成熟神经元。