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

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.