title: Induction of autophagic cell death in the rat brain caused by iron.
abstract: BACKGROUND
  The accumulation of iron in the brain is a hallmark of hemorrhagic stroke and several neurodegenerative diseases. Iron overload has been reported to induce brain injury through necrotic and apoptotic mechanisms. This study was taken to examine whether iron in the brain contributes to autophagic cell death.
  
  
  METHODS
  Sprague-Dawley rats received an intracerebral ventricular injection of either ferrous chloride or saline. The expression levels of autophagic markers were measured by Western blot analysis. Immunofluorescent double labeling was used to identify the cell types expressing Beclin 1. Transmission electron microscopy was performed to examine the ultrastructural changes in neural cells 1 day after ferrous iron injection.
  
  
  RESULTS
  Western blot analysis showed that the ratios of LC3-II to LC3-I and ATG5 levels were significantly upregulated at 6 hours and 1 day after ferrous iron injection. Beclin 1 expression was markedly elevated as early as 6 hours, reaching a peak at 24 hours and remaining elevated at 3 days after the injection. Beclin 1 immunoreactivity was located in both neurons and astrocytes under confocal microscopy. Induction of autophagic cell death was manifested by accumulation of autophagic vacuoles in the contralateral parietal cortex under transmission electron microscopy.
  
  
  CONCLUSIONS
  Our data showed that increased ferrous iron levels in the brain induced autophagic cell death. These results also suggest that autophagy form of programmed cell death may be a mechanism of brain injury in iron overload disorders.
authors.affiliation: Department of Neurosurgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Gao
authors.initials: G
authors.lastname: Chen
authors.forename: Chao-hui
authors.initials: CH
authors.lastname: Jing
authors.forename: Pan-pan
authors.initials: PP
authors.lastname: Liu
authors.forename: Di
authors.initials: D
authors.lastname: Ruan
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D057967:Infusions, Intraventricular; D007501:Iron / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007501:Iron