Deferoxamine reduces intracerebral hematoma-induced iron accumulation and neuronal death in piglets

Abstract

Background and purpose: Our previous studies found that deferoxamine reduces intracerebral hemorrhage (ICH)-induced brain injury in rats. The current study examined whether deferoxamine reduces brain injury in a piglet ICH model.

Methods: Pigs received an injection of autologous blood into the right frontal lobe. Deferoxamine (50 mg/kg, IM) or vehicle was administered 2 hours after ICH and then every 12 hours up to 7 days. Animals were killed 3 or 7 days later to examine iron accumulation, white matter injury, and neuronal death.

Results: ICH resulted in development of a reddish perihematomal zone, and iron accumulation, ferritin upregulation, and neuronal death within that zone. Deferoxamine reduced the perihematomal reddish zone, white matter injury, and the number of Perls', ferritin, and Fluoro-Jade C-positive cells.

Conclusions: Iron accumulation occurs in the piglet brain after ICH. Deferoxamine reduces ICH-induced iron buildup and brain injury in piglets.

Figure 1

Deferoxamine reduces reddish zone around hematoma at day 3 and day 7 in a pig ICH model. Values are means±SD, n=4, # p<0.01 vs. vehicle.

Figure 2

Iron histochemistry (Perls’ staining) and ferritin immunoreactivity in the brain after ICH. Asterisk indicates the hematoma. Insets in C and F: hematoxylin and eosin staining. Scale bar(A–H)=50 µm.

Figure 3

Fluoro-Jade C positive cells in the perihematomal area (A–C) and Luxol fast blue staining (E & F) after ICH. Part D shows four sampled fields for Fluoro-Jade C cell counting. Pigs had ICH and were treated with either vehicle or deferoxamine. Values are means±SD, n=4, *p<0.05, #p<0.01 vs. vehicle. Scale bar (A & B)=50 µm.