Long-term effects of experimental carotid stenosis on hippocampal infarct pathology, neurons and glia and amelioration by environmental enrichment.

ABSTRACT

Hippocampal atrophy and pathology are common in ageing-related disorders and associated with cognitive impairment and dementia. We explored whether environmental enrichment (EE) ameliorated the pathological sequelae in the hippocampus subsequent to chronic cerebral hypoperfusion induced by bilateral common carotid artery stenosis (BCAS). Seventy-four male C57BL/6 J mice underwent BCAS or sham surgery. One-week after surgery, mice were exposed to three different degrees of EE; either standard housing conditions (std), limited 3 -h exposure to EE per day (3 h) or full-time exposure to EE (full) for 3 months. Four months after surgery, the hippocampus was examined for the extent of vascular brain injury and neuronal and glial changes. Results showed that long-term BCAS induced strokes, most often in CA1 subfield, reduced 40-50 % CA1 neurons (P < 0.01) and increased microglia/macrophage in CA1-CA3 subfields (P < 0.02). Remarkably, both 3 h and full-time EE regimes attenuated hippocampal neuronal death and repressed recurrent strokes with complete prevention of larger infarcts in mice on full-time EE (P < 0.01). Full-time EE also reduced astrocytic clasmatodendrosis and microglial/macrophage activation in all CA subfields. Our results suggest that exposure to EE differentially reduces long-term hypoperfusive hippocampal damage. The implementation of even limited EE may be beneficial for patients diagnosed with vascular cognitive impairment.