Transcriptomic analysis of mouse brain microglia on aging-associated changes in response to cerebral ischemia

Senescence-associated alterations in microglia may have profound impact on cerebral homeostasis and stroke outcomes. However, the lack of a transcriptome-wide comparison between young and aged microglia in the context of ischemia limits our understanding of aging-related mechanisms. Herein, we performed bulk RNA sequencing analysis of microglia purified from cerebral hemispheres of young adult (10-week-old) and aged (18-month-old) mice 5 days after distal middle cerebral artery occlusion or sham operation. Considerable transcriptional differences were observed between young and aged microglia in healthy brains, indicating heightened chronic inflammation in aged microglia. Following stroke, the overall transcriptional activation was more robust in young microglia than in aged microglia. Gene clusters with functional implications in immune inflammatory responses, immune cell chemotaxis, tissue remodeling, and cell-cell interactions were markedly activated in microglia of young but not aged stroke mice. These alterations in microglial gene response may contribute to aging-driven vulnerability and poorer recovery after ischemic stroke.