Long Q, Hei Y, Luo Q, Tian Y, Yang J, Li J, Wei L, Liu W
Department of Neurosurgery, Xi'an Central Hospital, School of Medicine, Xi'an Jiao Tong University, No. 185 Houzai Gate of North Street, Xi'an 710003, PR China.
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No. 17 Changle West Road, Xi'an 710032, PR China.
Neuroscience. 2015 Dec 17;311:464-73. doi: 10.1016/j.neuroscience.2015.10.055. Epub 2015 Nov 3.
Bone marrow mesenchymal stem cells (BMSCs) transplantation can ameliorate cognitive impairment in chronic ischemic brain injury, but the underlying mechanism is poorly understood. It is considered that the hippocampus holds the capabilities of memory consolidation and spatial navigation, and the gamma amino butyric acid (GABA)ergic system plays an important role in the control of learning and memory processes. Herein, we investigated whether transplantation of BMSCs could improve cognitive impairment via regulating the hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion. Animals treated with permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) (a rat model of chronic cerebral hypoperfusion) received intravenous injections of BMSCs or saline as experimental group and control group I, the sham-operated rats received intravenous injections of BMSCs or saline as the sham group and control group II. Four weeks later, the Morris Water Maze was employed to evaluate the cognitive changes of each group, immunohistochemistry and western blotting was used to investigate the GABAergic system expression including GABA, glutamic acid decarboxylase 67 (GAD67) or GABA(B) receptor 1 (GABA(B)R1) in the hippocampus. Our results showed that the 2VO model presented decreased capacities of learning and memory and down-regulated the expression of GABA, GAD67 or GABA(B)R1 in the hippocampal CA1 subfield in comparison to the sham group (P<0.05), while administration of BMSCs (experimental group) manifested increased performances of learning sessions and probe tasks, as well as up-regulated expression of GABA, GAD67 or GABA(B)R1 compared with the control group I (P<0.05). Collectively, these findings suggest that transplantation of BMSCs is capable of improving cognitive impairment via up-regulating the hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion. Hence, BMSCs transplantation could serve as an important tool for cell therapy in chronic cerebral hypoperfusion disorders.
骨髓间充质干细胞（BMSCs）移植可改善慢性缺血性脑损伤中的认知障碍，但其潜在机制尚不清楚。人们认为海马体具有记忆巩固和空间导航的能力，γ-氨基丁酸（GABA）能系统在学习和记忆过程的控制中起重要作用。在此，我们研究了在慢性脑灌注不足大鼠模型中，BMSCs移植是否能通过调节海马体GABA能系统来改善认知障碍。接受双侧颈总动脉永久性闭塞（双血管闭塞，2VO）（慢性脑灌注不足大鼠模型）治疗的动物，分别静脉注射BMSCs或生理盐水作为实验组和对照组I，假手术大鼠静脉注射BMSCs或生理盐水作为假手术组和对照组II。四周后，采用Morris水迷宫评估各组的认知变化，采用免疫组织化学和蛋白质印迹法研究海马体中GABA能系统的表达，包括GABA、谷氨酸脱羧酶67（GAD67）或GABA(B)受体1（GABA(B)R1）。我们的结果表明，与假手术组相比，2VO模型表现出学习和记忆能力下降，海马体CA1亚区GABA、GAD67或GABA(B)R1的表达下调（P<0.05），而BMSCs给药组（实验组）与对照组I相比，学习环节和探索任务的表现有所提高，GABA、GAD67或GABA(B)R1的表达上调（P<0.05）。总的来说，这些发现表明，在慢性脑灌注不足大鼠模型中，BMSCs移植能够通过上调海马体GABA能系统来改善认知障碍。因此，BMSCs移植可作为慢性脑灌注不足疾病细胞治疗的重要工具。
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