An Enriched Environment Enhances Angiogenesis Surrounding the Cingulum in Ischaemic Stroke Rats

An enriched environment (EE) has been demonstrated to improve functional recovery in animal models of ischaemic stroke through enhancing vascular endothelial growth factor- (VEGF-) mediated neuroprotection accompanied by angiogenesis in the ischaemic hemisphere. Whether EEs also promote VEGF-mediate...

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Main Authors: Xueyan Shen, Lu Luo, Fei Wang, Kewei Yu, Hongyu Xie, Shan Tian, Gang Liu, Chunrong Bao, Yunhui Fan, Ying Xing, Nianhong Wang, Siyue Li, Li Liu, Qun Zhang, Yi Wu
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2020/8840319
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author Xueyan Shen
Lu Luo
Fei Wang
Kewei Yu
Hongyu Xie
Shan Tian
Gang Liu
Chunrong Bao
Yunhui Fan
Ying Xing
Nianhong Wang
Siyue Li
Li Liu
Qun Zhang
Yi Wu
author_facet Xueyan Shen
Lu Luo
Fei Wang
Kewei Yu
Hongyu Xie
Shan Tian
Gang Liu
Chunrong Bao
Yunhui Fan
Ying Xing
Nianhong Wang
Siyue Li
Li Liu
Qun Zhang
Yi Wu
author_sort Xueyan Shen
collection DOAJ
description An enriched environment (EE) has been demonstrated to improve functional recovery in animal models of ischaemic stroke through enhancing vascular endothelial growth factor- (VEGF-) mediated neuroprotection accompanied by angiogenesis in the ischaemic hemisphere. Whether EEs also promote VEGF-mediated neuroprotection and angiogenesis in the contralateral hemisphere remains unclear. Here, we explored the effect of EEs on VEGF expression and angiogenesis within the contralateral cerebral cortex in a rat middle cerebral artery occlusion/reperfusion (MCAO/r) model. We assessed the expression levels of platelet endothelial cell adhesion molecule-1 (CD31), VEGF, and endothelial nitric oxide synthase (eNOS) in the whole contralateral cerebral cortex using Western blotting assay but did not find an increase in the expression of CD31, VEGF, or eNOS in MCAO/r rats housed in EEs, which suggested that EEs did not enhance the overall expression of VEGF and eNOS or angiogenesis in the entire contralateral cortex. We further analysed the local effect of EEs by immunohistochemistry and found that in and around the bilateral cingulum in MCAO/r rats housed in EEs, haematopoietic progenitor cell antigen- (CD34-) positive endothelial progenitor cells were significantly increased compared with those of rats housed in standard cages (SCs). Further experiments showed that EEs increased neuronal VEGF expression surrounding the cingulum in MCAO/r rats and robustly upregulated eNOS expression. These results revealed that EEs enhanced angiogenesis, VEGF expression, and activation of the VEGF-eNOS pathway in and/or around the cingulum in MCAO/r rats, which were involved in the functional recovery of MCAO/r rats.
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spelling doaj-art-e5be8c3c7c44422395e2dc961c2378ef2025-08-20T03:26:17ZengWileyNeural Plasticity2090-59041687-54432020-01-01202010.1155/2020/88403198840319An Enriched Environment Enhances Angiogenesis Surrounding the Cingulum in Ischaemic Stroke RatsXueyan Shen0Lu Luo1Fei Wang2Kewei Yu3Hongyu Xie4Shan Tian5Gang Liu6Chunrong Bao7Yunhui Fan8Ying Xing9Nianhong Wang10Siyue Li11Li Liu12Qun Zhang13Yi Wu14Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaDepartment of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaDepartment of Hand Surgery, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaDepartment of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaDepartment of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaDepartment of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaDepartment of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaDepartment of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaDepartment of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaDepartment of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaDepartment of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaDepartment of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaDepartment of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaDepartment of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, ChinaAn enriched environment (EE) has been demonstrated to improve functional recovery in animal models of ischaemic stroke through enhancing vascular endothelial growth factor- (VEGF-) mediated neuroprotection accompanied by angiogenesis in the ischaemic hemisphere. Whether EEs also promote VEGF-mediated neuroprotection and angiogenesis in the contralateral hemisphere remains unclear. Here, we explored the effect of EEs on VEGF expression and angiogenesis within the contralateral cerebral cortex in a rat middle cerebral artery occlusion/reperfusion (MCAO/r) model. We assessed the expression levels of platelet endothelial cell adhesion molecule-1 (CD31), VEGF, and endothelial nitric oxide synthase (eNOS) in the whole contralateral cerebral cortex using Western blotting assay but did not find an increase in the expression of CD31, VEGF, or eNOS in MCAO/r rats housed in EEs, which suggested that EEs did not enhance the overall expression of VEGF and eNOS or angiogenesis in the entire contralateral cortex. We further analysed the local effect of EEs by immunohistochemistry and found that in and around the bilateral cingulum in MCAO/r rats housed in EEs, haematopoietic progenitor cell antigen- (CD34-) positive endothelial progenitor cells were significantly increased compared with those of rats housed in standard cages (SCs). Further experiments showed that EEs increased neuronal VEGF expression surrounding the cingulum in MCAO/r rats and robustly upregulated eNOS expression. These results revealed that EEs enhanced angiogenesis, VEGF expression, and activation of the VEGF-eNOS pathway in and/or around the cingulum in MCAO/r rats, which were involved in the functional recovery of MCAO/r rats.http://dx.doi.org/10.1155/2020/8840319
spellingShingle Xueyan Shen
Lu Luo
Fei Wang
Kewei Yu
Hongyu Xie
Shan Tian
Gang Liu
Chunrong Bao
Yunhui Fan
Ying Xing
Nianhong Wang
Siyue Li
Li Liu
Qun Zhang
Yi Wu
An Enriched Environment Enhances Angiogenesis Surrounding the Cingulum in Ischaemic Stroke Rats
Neural Plasticity
title An Enriched Environment Enhances Angiogenesis Surrounding the Cingulum in Ischaemic Stroke Rats
title_full An Enriched Environment Enhances Angiogenesis Surrounding the Cingulum in Ischaemic Stroke Rats
title_fullStr An Enriched Environment Enhances Angiogenesis Surrounding the Cingulum in Ischaemic Stroke Rats
title_full_unstemmed An Enriched Environment Enhances Angiogenesis Surrounding the Cingulum in Ischaemic Stroke Rats
title_short An Enriched Environment Enhances Angiogenesis Surrounding the Cingulum in Ischaemic Stroke Rats
title_sort enriched environment enhances angiogenesis surrounding the cingulum in ischaemic stroke rats
url http://dx.doi.org/10.1155/2020/8840319
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