Objective : Therapeutic hypothermia (TH) is increasingly being used to reduce secondary brain damage and intracranial pressure occurring in the acute phase after mechanical thrombectomy. However, the effect of TH on cognitive impairment has yet to be elucidated. In this work, we investigated whether TH can improve cognitive impairment in a mouse model of cerebral ischemia/reperfusion injury.Methods : Nine-week-old C57BL/6N mice (male) were randomly assigned to three groups: sham control, transient middle cerebral artery occlusion (tMCAO), and tMCAO with TH. One month after model induction, the expression levels of amyloid-β (Aβ 1-42), tau, and cyclophilin A were obtained using western blot analysis, while cognitive functioning was tested using open field and Y-maze, and the results were compared based on treatment group.Results : Compared to sham mice, mice with tMCAO exhibited significantly increased expression of Aβ (1-42) in the hippocampus, temporal cortex, and basal forebrain, along with significantly increased expression of tau and cyclophilin A in the basal forebrain. Further, mice with tMCAO exhibited decreased function of learning and memory. TH significantly decreased the Aβ (1-42) in the basal forebrain (0.84 ± 0.24 vs. 1.47 ± 0.29 in tMCAO), Aβ (1-42) in the hippocampus (0.73 ± 0.15 vs. 1.79 ± 0.58 in tMCAO), and tau in the basal forebrain (1.14 ± 0.21 vs. 1.58 ± 0.98 in tMCAO), but not that of cyclophilin A. Cognitive functions were significantly improved in mice with tMCAO and TH compared to those with tMCAO.
Conclusion :TH might be beneficial in ameliorating cognitive impairment after ischemia/reperfusion injury by reducing the expressions of Aβ (1-42) and tau.