Tang Yaohui, Wang Jixian, Lin Xiaojie, Wang Liuqing, Shao Bei, Jin Kunlin, Wang Yongting, Yang Guo-Yuan
Neuroscience and Neuroengineering Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
Department of Neurology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
J Cereb Blood Flow Metab. 2014 Jul;34(7):1138-47. doi: 10.1038/jcbfm.2014.61. Epub 2014 Apr 9.
Neural stem cells (NSCs) show therapeutic potential for ischemia in young-adult animals. However, the effect of aging on NSC therapy is largely unknown. In this work, NSCs were transplanted into aged (24-month-old) and young-adult (3-month-old) rats at 1 day after stroke. Infarct volume and neurobehavioral outcomes were examined. The number of differentiated NSCs was compared in aged and young-adult ischemic rats and angiogenesis and neurogenesis were also determined. We found that aged rats developed larger infarcts than young-adult rats after ischemia (P<0.05). The neurobehavioral outcome was also worse for aged rats comparing with young-adult rats. Brain infarction and neurologic deficits were attenuated after NSC transplantation in both aged and young-adult rats. The number of survived NSCs in aged rats was similar to that of the young-adult rats (P>0.05) and most of them were differentiated into glial fibrillary acidic protein(+) (GFAP(+)) cells. More importantly, angiogenesis and neurogenesis were greatly enhanced in both aged and young-adult rats after transplantation compared with phosphate-buffered saline (PBS) control (P<0.05), accompanied by increased expression of vascular endothelial growth factor (VEGF). Our results showed that NSC therapy reduced ischemic brain injury, along with increased angiogenesis and neurogenesis in aged rats, suggesting that aging-related microenvironment does not preclude a beneficial response to NSCs transplantation during cerebral ischemia.
神经干细胞（NSCs）在年轻成年动物的缺血治疗中显示出治疗潜力。然而，衰老对NSC治疗的影响在很大程度上尚不清楚。在这项研究中，在中风后1天将NSCs移植到老年（24个月大）和年轻成年（3个月大）大鼠体内。检测梗死体积和神经行为学结果。比较老年和年轻成年缺血大鼠中分化的NSCs数量，并确定血管生成和神经发生情况。我们发现，缺血后老年大鼠的梗死灶比年轻成年大鼠大（P<0.05）。与年轻成年大鼠相比，老年大鼠的神经行为学结果也更差。在老年和年轻成年大鼠中，NSC移植后脑梗死和神经功能缺损均有所减轻。老年大鼠中存活的NSCs数量与年轻成年大鼠相似（P>0.05），并且它们中的大多数分化为胶质纤维酸性蛋白（+）（GFAP（+））细胞。更重要的是，与磷酸盐缓冲盐水（PBS）对照组相比，移植后老年和年轻成年大鼠的血管生成和神经发生均显著增强（P<0.05），同时血管内皮生长因子（VEGF）的表达增加。我们的结果表明，NSC治疗减少了缺血性脑损伤，同时老年大鼠的血管生成和神经发生增加，这表明衰老相关的微环境并不妨碍在脑缺血期间对NSCs移植产生有益反应。
