Autophagic Cell Death Induced By Iron In The Rat Brain

Objective:The accumulation of iron in the brain is a hallmark of hemorrhagic stroke and some neurodegenerative diseases. Iron overload has been reported to cause brain injury through necrotic and apoptotic mechanisms. This study was taken to examine whether iron in the rat brain induces 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 Westernblot analysis, Immunofluorescent double labeling was used to identify the cell types expressing Beclin1.Results:Western blot analysis showed that the ratios of LC3-II to LC3-I and ATG5levels were significantly upregulated at6hours and1day after ferrous iron injection. Beclin1expression was markedly elevated as early as6hours, reaching a peak at24hours and remaining elevated at3days after the injection. Beclin1immunoreactivity was located in both neurons and astrocytes under confocal 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.