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.

海马萎缩和病理在衰老相关疾病中很常见，并与认知障碍和痴呆有关。我们探讨了环境富集（EE）是否可以改善双侧颈总动脉狭窄（BCAS）引起的慢性脑灌注不足引起的海马病理后遗症。 74 只雄性 C57BL/6 J 小鼠接受了 BCAS 或假手术。手术后一周，小鼠暴露于三种不同程度的EE；标准住房条件 (std)、每天限制 3 小时暴露于 EE (3 小时) 或全职暴露于 EE (全部) 3 个月。手术后四个月，检查海马体的血管性脑损伤程度以及神经元和神经胶质的变化。结果显示，长期 BCAS 诱发中风（最常见于 CA1 亚区），导致 CA1 神经元减少 40-50%（P < 0.01），CA1-CA3 亚区小胶质细胞/巨噬细胞增加（P < 0.02）。值得注意的是，3 小时和全时 EE 方案均可减轻海马神经元死亡并抑制复发性中风，并完全预防全时 EE 小鼠中较大的梗塞 (P < 0.01)。全职 EE 还减少了所有 CA 亚区的星形胶质细胞增生和小胶质细胞/巨噬细胞激活。我们的结果表明，接触 EE 可以不同程度地减少长期低灌注海马损伤。即使是有限的 EE 实施也可能对诊断为血管性认知障碍的患者有益。