Background: The presence of extracorpuscular hemoglobin (Hb) exacerbates brain damage following intracerebral hemorrhage (ICH). Systemically, haptoglobin (Hp) is an acute phase glycoprotein that reduces brain injury by binding to extracellular Hb, which stabilizes the protein and prevents further toxic reactions. However, the properties of Hp within the brain during ICH are not well understood. This study aims to investigate the acute and chronic effects of haptoglobin deletion following ICH and the possibility that age influences the recovery outcomes.
Methods: The ICH was induced in young and older aged (WT) controls and Hp-/- C57BL/6 mice using the autologous whole blood and collagenase injection models. Behavioral assessments of neurological deficit scoring, open field locomotor activity, and rotarod were conducted to investigate functional outcomes at 1d, 2d, 3d, 4d, 7d, and 10d. Various anatomical outcomes were measured through the staining for specific biomarkers following animal sacrifice at 3d and 10d.
Results: At 3d, Hp-/- mice display 36.7±6.9% smaller lesions, 35.8 ± 9.5% less residual blood volume and 36.9±6.5% less tissue injury. At 10d, young Hp-/- mice show significant reduction in lesion volume. Behavioral assessments exhibit a reduction in neurological deficits in Hp mice. Similarly, young and old Hp-/- mice show significant differences in neurological deficit scores and open field locomotor activity at 3d and 10d. Additionally, Hp-/- mice display significantly less heme oxygenase 1 expression, less iron, and, less blood-brain barrier breakdown at 3d conversely, no significant differences are observed at 10d. Furthermore, Hp-/- mice show a reduction in hematomal vascular endothelial growth factor expression and ipsilateral motor cortex expression at 3d. Additionally, ipsilateral thalamic astrogliosis was less in young Hp-/- mice but no significance observed at 10d.
Conclusion: The results of this study display the acute and chronic ameliorating effects of haptoglobin deletion in mice following ICH. Initially, Hp-/- mice have significant reductions in brain injury and later, perform similarly and occasionally better than WT controls.