Cerebral microinfarcts represent the most prevalent form of ischemic braininjury in the elderly, particularly among those suffering from dementia,Alzheimer’s disease, and vascular risk factors. Despite their commonality,effective treatments have remained elusive. Herein, a novel treatmentutilizing a polymer-formulated nerve growth factor capable of crossing theblood-brain barrier is reported, which effectively reduced oxidative stress andneuronal apoptosis, reshaped microglia polarization at infarct sites, anddecreased the overall microinfarct burden, leading to notable improvementsin behavioral and cognitive functions in a mouse model. This work provides apromising new avenue for the treatment of cerebral microinfarcts and otherneurodegenerative diseases.