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

Xueyan Shen,Ying Xing,Li Liu,Shan Tian,Yi Wu,Gang Liu,Hongyu Xie,Qun Zhang,Nianhong Wang,Siyue Li,Yunhui Fan,Lu Luo,Chunrong Bao,Kewei Yu,Fei Wang,Rubin Wang

doi:10.1155/2020/8840319

Abstract

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.

Highlights

After unilateral cerebral injury due to ischaemic factors, the cerebral hemisphere of the healthy side can compensatively control the affected limb through a potential neural pathway [1]
We investigated the effects of EEs on CD31, vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS) protein expression in the contralateral cortical tissue of middle cerebral artery occlusion/reperfusion (MCAO/r) adult rats using Western blotting assay
It is possible that the total amount of cortical protein remained unchanged, but the local distribution changed

Summary

Introduction

After unilateral cerebral injury due to ischaemic factors, the cerebral hemisphere of the healthy side can compensatively control the affected limb through a potential neural pathway [1]. This functional compensation of the healthy side is an important way to restore limb function after unilateral cerebral ischaemia. An enriched environment is a combination of stimuli, including a broad range of activities, increased numbers of social partners, and enriched objects and tactile stimuli [2]. Increasing evidence shows that EEs have neuroprotective benefits in MCAO animal models [8, 9]

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Conclusion