Deferoxamine attenuates white matter injury in a piglet intracerebral hemorrhage model

Abstract

Background and purpose: Deferoxamine reduces neuronal death in a piglet model of intracerebral hemorrhage (ICH). This study examined the effect of deferoxamine on perihematomal white matter edema in piglets.

Methods: ICH was induced by an injection of autologous blood into the right frontal lobe of piglets. In the first part of study, the time course of edema formation was determined. In the second part, the effects of deferoxamine on ICH-induced white matter edema, tumor necrosis factor α, and receptor-interacting protein kinase 1 were examined.

Results: ICH resulted in marked brain edema and increased tumor necrosis factor α and receptor-interacting protein kinase 1 levels in white matter. Systemic treatment with deferoxamine markedly reduced white matter tumor necrosis factor α and receptor-interacting protein kinase 1 levels and attenuated white matter edema after ICH.

Conclusions: Deferoxamine reduces white matter edema, tumor necrosis factor α, and receptor-interacting protein kinase 1 levels after ICH in piglets, suggesting deferoxamine is a potential effective therapeutic agent for patients with ICH.

Keywords: brain edema; cerebral hemorrhage; deferoxamine; receptor-interacting protein serine-threonine kinase 1; tumor necrosis factor-alpha.

Figures

Figure 1

Hematoma resolution (A) and brain water content in white matter (B) at different times after ICH. Values are mean ± SD. *p<0.05 vs. the contralateral side.

Figure 2

(A) Brain water content in white matter 3 days after ICH with DFX or vehicle (Veh) treatment. (B) TNF-α levels in white matter 3 days after ICH with DFX or vehicle treatment. Values are mean ± SD. *p<0.05 vs. vehicle treatment.

Figure 3

(A) Time course of RIPK1 in white matter after ICH. Values are mean ± SD. #p<0.05 vs. sham. (B) White matter RIPK1 levels after ICH with DFX or vehicle treatment. Values are mean ± SD. *p<0.05 vs. the other groups.