Abstract T P232: Brain CD47 Expression in a Piglet Model of Intracerebral Hemorrhage

Abstract

Differentiation 47 (CD47) has a role in ischemic brain injury and phagocytosis. The role of CD47 in intracerebral hemorrhage (ICH) has not been investigated and the current study examined brain CD47 expression in a piglet ICH model. Methods: Piglets received a blood injection or needle insertion into the right frontal lobe and were euthanized at different times to examine CD47 expression. Piglets were also treated with an iron chelator, deferoxamine, (50 mg/kg, i.m.) or vehicle and euthanized at day-3 to examine the effects on CD47. Results: ICH resulted in upregulation of brain CD47 in both white and grey matter by both immunohistochemistry and Western blot. A time-course showed ICH-induced CD47 upregulation from 4 hours to day-14. ICH-induced CD47 upregulation peaked at day-3. CD47 positive cells were neurons, microglia/macrophage and oliogodendrocytes. Systemic treatment with deferoxamine (started at 2 hours after ICH and every 12 hours for 3 days), an iron chelator, reduced CD47 levels in the ipsilateral white matter (CD47/beta-actin: 0.35 ± 0.08 vs. 0.73 ± 0.09 in vehicle-treated pigs, p<0.01) and grey matter (0.64 ± 0.16 vs.1.19 ± 0.20 in vehicle-treated pigs, p<0.01) at day-3 after ICH. CD47 expression on erythrocytes was reduced at 24 hours compared with that at 4 hours after ICH (p<0.05), and significant erythrophagocytosis was present in the clot. Conclusion: CD47 expression was increased in the perihematomal white and grey matter and was decreased in the clot after ICH. Alterations in CD47 expression may play a role in parenchymal injury and hematoma resolution. Deferoxamine and iron may modulate CD47 expression. Key words: cerebral hemorrhage, CD47, deferoxamine, erythrophagocytosis, piglets