title: BMSCs transplantation improves cognitive impairment via up-regulation of hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion.
abstract: 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.
authors.affiliation: 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. Electronic address: lonva@live.cn.
authors.forename: Q
authors.initials: Q
authors.lastname: Long
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No. 17 Changle West Road, Xi'an 710032, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Hei
authors.affiliation: 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.
authors.forename: Q
authors.initials: Q
authors.lastname: Luo
authors.affiliation: 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.
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No. 17 Changle West Road, Xi'an 710032, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No. 17 Changle West Road, Xi'an 710032, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D002340:Carotid Artery Diseases; D002465:Cell Movement / Q000502:physiology; D002908:Chronic Disease; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D008297:Male; D018782:Maze Learning / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D015854:Up-Regulation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid
keywords: GABAergic system; bone marrow mesenchymal stem cells; chronic cerebral hypoperfusion; hippocampus