Abstract
JOURNAL/nrgr/04.03/01300535-202509000-00022/figure1/v/2024-11-05T132919Z/r/image-tiff Poststroke cognitive impairment is a major secondary effect of ischemic stroke in many patients; however, few options are available for the early diagnosis and treatment of this condition. The aims of this study were to (1) determine the specific relationship between hypoxic and α-synuclein during the occur of poststroke cognitive impairment and (2) assess whether the serum phosphorylated α-synuclein level can be used as a biomarker for poststroke cognitive impairment. We found that the phosphorylated α-synuclein level was significantly increased and showed pathological aggregation around the cerebral infarct area in a mouse model of ischemic stroke. In addition, neuronal α-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia, suggesting that hypoxia is the underlying cause of α-synuclein-mediated pathology in the brains of mice with ischemic stroke. Serum phosphorylated α-synuclein levels in patients with ischemic stroke were significantly lower than those in healthy subjects, and were positively correlated with cognition levels in patients with ischemic stroke. Furthermore, a decrease in serum high-density lipoprotein levels in stroke patients was significantly correlated with a decrease in phosphorylated α-synuclein levels. Although ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury, some of them exhibited decreased cognitive function and reduced phosphorylated α-synuclein levels. Taken together, our results suggest that serum phosphorylated α-synuclein is a potential biomarker for poststroke cognitive impairment.