title: Enriched environment induces angiogenesis and improves neural function outcomes in rat stroke model.
abstract: Increasing evidence shows that exposure to an enriched environment (EE) after cerebral ischemia/reperfusion injury has neuroprotective benefits in animal models, including enhancing functional recovery after ischemic stroke. However, the mechanism underlying this effect remains unclear. To clarify this critical issue, the current study investigated the effects of EE on the improvement of damaged neural function and the induction of angiogenesis. Adult rats were subjected to ischemia induced by middle cerebral artery occlusion followed by reperfusion. Neurological status scores were used to evaluate neural function on postoperative days 2, 7, and 14. A beam-walking task was used to test the recovery of motor behavior on postoperative days 2, 5, 10, and 15. We also used a Morris water maze task to examine whether EE protected learning and memory performance. The specific marker of angiogenesis of CD31 was examined by western blot. Angiogenesis around the peri-infarction region was assayed by laser scanning confocal microscopy (LSCM) after 14 days of EE exposure starting 24h after ischemia. Neurological status scores of animals in the EE group were significantly higher than those in the standard housing condition (SC) control group from the seventh day after ischemic. EE accelerated the recovery of motor coordination and integration and also improved learning and memory performance after cerebral ischemia. Furthermore, EE increased CD31 levels and promoted angiogenesis of cortex in the peri-infarction region compared to the SC group. Neural function outcomes are positively correlated with post-ischemia angiogenesis. These findings suggest that EE plays an important role in the recovery of damaged neural function via regulation of angiogenesis after ischemia.
authors.affiliation: Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
authors.forename: Kewei
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China; The Yonghe Branch of Huashan Hospital, Fudan University, Shanghai 200436, China; Department of Sports Medicine and Rehabilitation, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Rehabilitation Medicine, Jing'an District Centre Hospital of Shanghai, 200040, China. Electronic address: doctoryu8000@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China; The Yonghe Branch of Huashan Hospital, Fudan University, Shanghai 200436, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Rehabilitation Medicine, Jing'an District Centre Hospital of Shanghai, 200040, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China; Department of Sports Medicine and Rehabilitation, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Clinical Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Shenyi
authors.initials: S
authors.lastname: Kuang
authors.affiliation: Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Sports Medicine and Rehabilitation, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: rphu79@163.com.
authors.forename: Ruiping
authors.initials: R
authors.lastname: Hu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004777:Environment; D006799:Housing, Animal; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D018782:Maze Learning; D008568:Memory; D018613:Microscopy, Confocal; D009043:Motor Activity; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000150:complications / Q000628:therapy*; D020521:Stroke / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1
keywords: Angiogenesis; CD31; Enriched environment; Ischemia; Neural function; Neuroprotection