Abstract: Reports have shown that damage to the adult brain can result in adaptive changes in regions adjacent to or surrounding the site of the principal injury, and that these changes may be modulated by rehabilitation training. An enriched environment has been shown to improve the cognitive, behavioral, and histopathological outcomes following focal cerebral ischemia and head trauma. Morphological changes in areas adjacent to the injury site have been reported following damage to the adult brain. In transient global cerebral ischemia, changes are observed in neuronal and non-neuronal cells in the regions that surround the primary injury site, including dendritic restructuring, reactive changes in glia, reactive synaptogenesis, and enhanced neurogenesis. The purpose of this study was to investigate the effects of an enriched environment on the structural modification of synaptic interface and PSD-95 mRNA of rats following transient focal cerebral ischemia, and elucidate the underlying mechanism.
Seventy adult male Sprague-Dawley rats (weight: 250~300 g) were included in this study. A transient ischemic model of rats was established by occluding the right middle cerebral artery (MCAO) with a nylon filament (diameter 0.234 mm). Three days following ischemia or sham surgery, the rats were randomly assigned to the following environmental conditions for 14 days: enriched environment housing (ischemia enriched environment (IE) and sham enriched environment (SE)) or standard environment housing (ischemia standard environment (IS) and sham standard environment (SS)). In order to observe (a) the changes in learning and memory and (b) the ultrastructure of the frontal cortex and hippocampus of the rats following focal cerebral ischemia, the Morris water maze test and transmission electron microscopy, and morphological measurements, respectively, were used in the present study. Simultaneously, the expression of PSD-95 mRNA was measured by RT-PCR.
The results of the water maze revealed that although cerebral ischemia significantly damaged the ability of spatial learning and memory, environmental enrichment significantly improved the memory damage induced by cerebral ischemia. Meanwhile, environmental enrichment restrained the reduction of the synaptic density caused by cerebral ischemia, particularly in the frontal cortex. Further, environmental enrichment also reversed the changes in synaptic interface parameters caused by cerebral ischemia at different levels, particularly increasing the thickness of postsynaptic density and decreasing the synaptic cleft width. Furthermore, environmental enrichment significantly up-regulated the expression of PSD-95 mRNA in the ipsilateral cortex and hippocampus of MCAO rats.
These results suggest that the enriched environment significantly promoted spatial learning and memory in MCAO rats. The amelioration of structural modification of the synaptic interface and up-regulation of the expression of PSD-95 mRNA were also involved

Key words: enriched environment, transient focal cerebral ischemia, structural modification of synaptic interface, PSD-95 mRNA