Effect of enriched environment on angiogenesis and neurological functions in rats with focal cerebral ischemia.
The purpose of this study was to investigate the effect of enriched environment (EE) on cerebral angiogenesis after ischemia-reperfusion injury. Middle cerebral artery occlusion (MCAO) followed by reperfusion was performed in rats to set up an animal model of ischemia-reperfusion injury. In a set of behavioral tests, we demonstrated that the animals in the IEE (ischemia + enriched environment) group exhibited significantly improved neurological functions compared to those in the standard housing condition group. In consistent with the functional tests, smaller infarction volumes were observed in the animals of IEE group. Laser scanning confocal microscopy and 3D quantitative analysis of cerebral microvessels revealed that EE treatment increased the total vessel surface area and number of branch point in the ischemic boundary zone. IgG extraction assay showed that the blood brain barrier (BBB) leakage in the ischemic brain was attenuated after EE treatment. EE treatment also enhanced endothelial cells (ECs) proliferation and increased the expression levels of VEGF and its receptor Flk-1 after ischemia-reperfusion injury. Analyses of Spearman's correlation coefficients indicated a correlation of mNSS scores with enhanced cerebral angiogenesis. Together, the results suggest that EE treatment-induced cerebral angiogenesis may contribute to the improved neurological outcome of stroke animals after ischemia-reperfusion injury.
Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Xin
X
Zhang
Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Xiu-Ping
XP
Chen
Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Jun-Bin
JB
Lin
Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, China.
Yu
Y
Xiong
Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: weijingliaorehab@163.com.
Wei-Jing
WJ
Liao
Department of Physiology, Center for Brain Clinic, Zhongnan Hospital, Collaborative Innovation Center for Brain Science, School of Medicine, Wuhan University, Wuhan 430071, China. Electronic address: qwan@whu.edu.cn.
Qi
Q
Wan
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000534:rehabilitation*; D002199:Capillary Permeability; D049109:Cell Proliferation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology; D004777:Environment; D006799:Housing, Animal; D007074:Immunoglobulin G / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D009043:Motor Activity; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000534:rehabilitation*; D020521:Stroke / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D000071939:Stroke Rehabilitation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D007074:Immunoglobulin G; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D040301:Vascular Endothelial Growth Factor Receptor-2
Angiogenesis; Endothelial cells; Enriched environment; MCAO; VEGF