Enhanced white matter reorganization and activated brain glucose metabolism by enriched environment following ischemic stroke: Micro PET/CT and MRI study

Enriched environment (EE) is an effective rehabilitative protocol designed to enhance sensorimotor, cognitive and social stimulation. Current understanding of neuronal remodeling after EE intervention mainly derived from conventional histological methods. The efficacy of EE treatment on post-stroke brain reorganization still needed to be elucidated in vivo. This study aimed to examine the effects of post-ischemic EE treatment on the brain remodeling using magnetic resonance imaging (MRI) and 18F-FDG positron emission tomography (PET). Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) and housed in standard environment (SE) or EE for consecutive 30 days. Cognitive testing was performed using the Morris water maze. White matter structural modifications were detected by MRI combined with histological analysis. In addition, PET scanning with 18F-FDG as a molecular probe was conducted to detect brain energy metabolism. Our results showed that EE significantly mitigated MCAO-induced impairments in spatial learning and memory, attenuated brain atrophy, protected white matter integrity, and enhanced white matter reorganization coupled with promoting oligodendrogenesis. In parallel to these findings, PET-MRI fused images showed that EE remarkably elevated regional cerebral metabolic rates of glucose in the lesioned sensorimotor cortex, striatum and corpus callosum/external capsule. More importantly, a strong correlation was demonstrated between glucose utilization and diffusion tensor imaging indices in the corresponding brain regions. The data herein indicated that improved global metabolism of glucose was a critical step in the reorganization of the white matter following post-stroke EE intervention. Although EE did not produce beneficial effects on restoring brain infarct volume, the broad range of structural and functional benefits observed in the present study raised the interesting possibility that EE might be an effective rehabilitative strategy for ischemic stroke.