Search

Background and Purpose: Stroke can cause memory dysfunction. Long-term memory dysfunction of mice with tibia fracture (BF)+stroke is associated with accumulation of CD68 + cells in the hippocampus, which can be alleviated by activation of alpha-7 nicotinic acetylcholine receptor (α-7 nAchR). Microglia maintain normal memory via removing excessive synapses. We hypothesize that aged mice would develop long-lasting memory dysfunction after stroke, which is associated with increased CD68 + cells and synapses removing in the hippocampi. Methods: Permanent distal middle cerebral artery occlusion (pMCAO) was performed in young (2-month-old) and aging (15-18-month-old) mice, or 6 hours before pMCAO in young mice. The memory functions were analyzed weekly for 8 weeks by Y-maze and at 8 weeks post pMCAO by NOR tests. Atrophic volumes, CD68 + cells and microglial phagocytosis of synapses were quantified at 8 weeks after pMCAO. Results: Aged mice had larger atrophic volumes, more CD68 + cells in the hippocampi ipsilateral to stroke side than young mice, and also had more CD68 + cells in the ipsilateral hippocampus than the contralateral. In Y-maze test, the aged stroke mice made fewer spontaneous alternations from 3 to 8 weeks after pMCAO than the young stroke mice and sham aged mice. In NOR test, aged stroke mice spent less time on the novel object than young stroke mice and sham aged mice. α-7 nAchR agonist treatment reduced the number of CD68 + cells in the hippocampi in the BF+stroke mice. Almost all CD68 + cells were synaptophysin positive. Therefore, increased CD68 + cells in the ipsilateral hippocampus will increase synaptic removal. Reduction of neuroinflammation could reduce synaptic loss and improve post-stroke memory function. Conclusions: Increased CD68 + cells in the hippocampus is associated with long-lasting post-stroke memory dysfunction in aged mice, and reduced neuroinflammation could improve post-stroke memory function.