Yoshiya Kazuhisa, Tanaka Hiroshi, Kasai Kousuke, Irisawa Taro, Shiozaki Tadahiko, Sugimoto Hisashi
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
J Neurotrauma. 2003 Nov;20(11):1147-62. doi: 10.1089/089771503770802844.
Neural stem cells, which reside in the subventricular zone (SVZ) and dentate gyrus (DG) of adult mammals, give rise to new neurons throughout life. However, these neural stem cells do not appear to contribute to regeneration in the damaged central nervous system. Following traumatic brain injury (TBI) in adult rats, the number of proliferating cells labeled with bromodeoxyuridine (BrdU) is significantly increased in the bilateral SVZ and DG; however, these proliferating cells do not contribute to effective regeneration in the damaged area. To gain insight into the molecular mechanisms of these biological actions, changes in gene expression in the SVZ after brain trauma were examined by cDNA microarray. Of 9,596 genes screened, 97 were upregulated and 204 were downregulated. Classifying these genes according to their function suggests that TBI affects a broad range of cellular functions. The validity of the data was confirmed by RT-PCR. The expression of some genes localized in the SVZ was confirmed by in situ hybridization. This combined strategy is effective for comprehensive analysis of the pathophysiological changes in the SVZ after brain injury and should contribute to the understanding of the molecular events that occur after injury. In the future, this may enable regeneration of the damaged central nervous system.
神经干细胞存在于成年哺乳动物的脑室下区(SVZ)和齿状回(DG)中,终生都能产生新的神经元。然而,这些神经干细胞似乎并未对受损的中枢神经系统的再生起到作用。成年大鼠遭受创伤性脑损伤(TBI)后,双侧SVZ和DG中用溴脱氧尿苷(BrdU)标记的增殖细胞数量显著增加;然而,这些增殖细胞对受损区域的有效再生并无贡献。为深入了解这些生物学作用的分子机制,通过cDNA微阵列检测了脑创伤后SVZ中的基因表达变化。在筛选的9596个基因中,97个基因上调,204个基因下调。根据功能对这些基因进行分类表明,TBI影响广泛的细胞功能。数据的有效性通过RT-PCR得到证实。一些定位于SVZ的基因的表达通过原位杂交得到证实。这种联合策略对于全面分析脑损伤后SVZ的病理生理变化是有效的,并且应该有助于理解损伤后发生的分子事件。未来,这可能使受损的中枢神经系统实现再生。