Temporal changes in blood haptoglobin levels after ischemic stroke in mice and humans.

Abstract

BACKGROUND: Our previous animal study demonstrated that repeated administration of haptoglobin (Hp) improved functional outcomes after ischemic stroke. However, the dynamics of endogenous blood Hp following ischemic stroke remain unclear. Therefore, we performed an exploratory study examining temporal changes in endogenous blood Hp levels and functional outcomes in mice and humans. METHODS: Serum Hp levels were measured in male mice using a middle cerebral artery occlusion (MCAO) model. In a retrospective clinical study, serum Hp levels were measured at admission (Day 0), Day 2-3, and Day 6-7 in 30 patients with ischemic stroke, stratified by outcome (favorable: modified Rankin Scale [mRS] score≤3; unfavorable: mRS score>3). RESULTS: In male mice, survival declined markedly between Days 6 and 7 after MCAO. Neurological deficits and loss of body weight did not improve until Day 7 after MCAO. Serum Hp levels peaked on Day 1 after MCAO and declined significantly by Day 7. In patients, serum Hp levels were similar on Days 0 and 2-3 but were significantly lower on Day 6-7 than on the earlier time points. When comparing the favorable and unfavorable outcome groups, Hp levels remained stable in the favorable outcome group, whereas they progressively declined in the unfavorable outcome group, resulting in a significant difference between the groups on Day 6-7. In both mice and humans, declining Hp levels paralleled worsening functional outcomes after ischemic stroke. CONCLUSION: Similar temporal patterns of Hp changes were observed in mice and humans, suggesting that Hp levels may reflect systemic inflammation and correlate with short-term functional status after ischemic stroke.