title: Environmental enrichment synergistically improves functional recovery by transplanted adipose stem cells in chronic hypoxic-ischemic brain injury.
abstract: We investigated the effects of environmental enrichment (EE) on the function of transplanted adipose stem cells (ASCs) and the combined effect of EE and ASC transplantation on neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in 7-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At 6 weeks of age, the mice were randomly injected with either ASCs or PBS into the striatum and were randomly assigned to either EE or standard cages (SC), comprising ASC-EE (n=18), ASC-SC (n=19), PBS-EE (n=12), PBS-SC (n=17), and untreated controls (n=23). Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. The fate of transplanted cells and the levels of endogenous neurogenesis, astrocyte activation, and paracrine factors were also measured. As a result, EE and ASC transplantation synergistically improved rotarod latency, forelimb-use asymmetry, and grip strength compared to those of the other groups. The number of engrafted ASCs and βIII-tubulin(+) neurons derived from the transplanted ASCs was significantly higher in mice in EE than those in SC. EE and ASC transplantation also synergistically increased BrdU(+)βIII-tubulin(+) neurons, GFAP(+) astrocytic density, and fibroblast growth factor 2 (FGF2) level but not the level of CS-56(+) glial scarring in the striatum. In conclusion, EE and ASC transplantation synergistically improved neurobehavioral functions. The underlying mechanisms of this synergism included enhanced repair processes such as higher engraftment of the transplanted ASCs, increased endogenous neurogenesis and astrocytic activation coupled with upregulation of FGF2.
authors: Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors: Jung Hwa
authors: JH
authors: Seo
authors: Hyongbum
authors: H
authors: Kim
authors: Eun Sook
authors: ES
authors: Park
authors: Jong Eun
authors: JE
authors: Lee
authors: Dong Wook
authors: DW
authors: Kim
authors: Hyun Ok
authors: HO
authors: Kim
authors: Sang Hee
authors: SH
authors: Im
authors: Ji Hea
authors: JH
authors: Yu
authors: Ji Yeon
authors: JY
authors: Kim
authors: Min-Young
authors: MY
authors: Lee
authors: Chul Hoon
authors: CH
authors: Kim
authors: Sung-Rae
authors: SR
authors: Cho
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000503:physiopathology / Q000637:transplantation*; D000368:Aged; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004777:Environment; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D055495:Neurogenesis / Q000187:drug effects; D020127:Recovery of Function; D033581:Stem Cell Transplantation / Q000379:methods*