Enriched Environment Promotes Cognitive Function Recovery following Cerebral Ischemic Injury via Upregulating GABAergic and Glutamatergic Systems in the Contralateral Hippocampus.

Yuyang Wang,Junfa Wu,Hongyu Xie,Liping Wang,Chuanjie Wang,Yi Wu,Feng Zhang

doi:10.1155/2020/8850119

Abstract

Poststroke cognitive impairment severely affects the long-term recovery of patients. However, it remains unknown whether an enriched environment can remodel contralateral hippocampal function and promote cognitive function recovery after cerebral ischemic injury. To further explore, 36 C57BL/6 mice that underwent permanent middle cerebral artery occlusion (pMCAO) were randomly assigned to three groups: enriched environment (EE), standard condition (SC), and sham surgery (Sham). After 21 days of intervention, the Morris water maze and step-through test was utilized for testing the cognitive function of the mice, cresyl violet staining for measuring the degree of atrophy in the hippocampal tissues, and western blotting for quantitating the expression levels of GA1B, GAD67, and NR2B, and immunohistochemistry for levels of NR2B in the CA1 region of the contralateral hippocampus. The results showed that cognitive function-related behavioral performance decreased in the SC group, and performance was better in the EE group than that in the SC group (p < 0.01); no significant difference in the degree of contralateral cerebral atrophy was observed between the EE and SC groups (p > 0.05); levels of GA1B, GAD67, and NR2B in the contralateral hippocampus were significantly higher in the EE group than those in the SC group (p < 0.01); and the level of NR2B in the CA1 region of the contralateral hippocampus significantly increased in the EE group compared to the SC group (p < 0.01). We believe that contralateral hippocampal function is inhibited after cerebral ischemic injury, further affecting cognitive function. However, enriched environment can upregulate GABAergic and glutamatergic systems in the contralateral hippocampus to promote cognitive function recovery after cerebral ischemic injury.

Highlights

Cognitive impairment is one of the most common complications of stroke [1]. e long-term effects of poststroke cognitive impairment is much more severe than those of physical impairment and can cause patients to experience difficulties in connection with the perception and adaptation to the external environment
We found that the permanent middle cerebral artery occlusion (pMCAO) model may cause persistent cognitive impairment, and both GABAergic nervous system and glutamatergic receptors in the contralateral hippocampus of cerebral ischemic injury were inhibited
EE promotes recovery of cognitive function after cerebral ischemic injury that may in part be mediated by upregulating GA1B, GAD67, and N-methyl-D-aspartate receptor 2B (NR2B) which were relevant to the aforementioned systems in the contralateral hippocampus

Summary

Introduction

Cognitive impairment is one of the most common complications of stroke [1]. e long-term effects of poststroke cognitive impairment is much more severe than those of physical impairment and can cause patients to experience difficulties in connection with the perception and adaptation to the external environment. A previous study found that EE’s role in the improvement of cognitive impairment may be associated with restoration of hippocampal neuronal regeneration, increasing the length of myelinated nerve fibers in the hippocampus, or promoting cerebral blood vessels and blood flow in areas around ischemic cortical regions. EE demonstrated some benefits in various animal models of brain diseases, including improving cognition, delaying disease progression, increasing cell plasticity, and expression levels of related proteins [7]. We assumed that contralateral hippocampal GABAergic and glutamatergic systems-related proteins GAD67 (glutamic acid decarboxylase-67), GA1B (GABAB receptor 1), and NR2B (N-methyl-D-aspartate receptor 2B) were upregulated by EE to further reveal the effects and mechanisms by which EE can improve cognitive function after cerebral ischemia [9,10,11]

Materials and Methods

Results

Findings

Discussion