Gu Yuxiang, Hua Ya, He Yangdong, Wang Lin, Hu Hua, Keep Richard F, Xi Guohua
Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Acta Neurochir Suppl. 2011;111:123-8. doi: 10.1007/978-3-7091-0693-8_20.
Cerebral iron overload causes brain injury after intracerebral hemorrhage (ICH) in rats and pigs. The current study examined whether an iron chelator, deferoxamine, can reduce ICH-induced DNA damage in pigs. Pigs received an injection of autologous blood into the right frontal lobe. Deferoxamine (50 mg/kg, i.m.) or vehicle was given 2 h after ICH and then every 12 h up to 7 days. Animals were killed at day 3 or day 7 after ICH to examine iron accumulation and DNA damage. We found that ICH resulted in the development of a reddish perihematomal zone, with iron accumulation and DNA damage within that zone. Deferoxamine treatment reduced the perihematomal reddish zone, and the number of Perls' (p<0.01) and TUNEL (p<0.01) positive cells. In conclusion, iron accumulates in the perihematomal zone and causes DNA damage. Systemic deferoxamine treatment reduces ICH-induced iron overload and DNA damage in pigs.
脑铁过载在大鼠和猪的脑出血(ICH)后会导致脑损伤。本研究检测了铁螯合剂去铁胺是否能减轻猪ICH诱导的DNA损伤。给猪的右额叶注射自体血。脑出血后2小时给予去铁胺(50mg/kg,肌肉注射)或赋形剂,然后每12小时给药一次,持续7天。在脑出血后第3天或第7天处死动物,以检测铁蓄积和DNA损伤。我们发现,脑出血导致血肿周围出现红色区域,该区域有铁蓄积和DNA损伤。去铁胺治疗减少了血肿周围的红色区域以及Perls(p<0.01)和TUNEL(p<0.01)阳性细胞的数量。总之,铁在血肿周围区域蓄积并导致DNA损伤。全身性去铁胺治疗可减轻猪ICH诱导的铁过载和DNA损伤。