RT Journal Article
SR Electronic
T1 Chelation of Mitochondrial Iron Prevents Seizure-Induced Mitochondrial Dysfunction and Neuronal Injury
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 11550
OP 11556
DO 10.1523/JNEUROSCI.3016-08.2008
VO 28
IS 45
A1 Li-Ping Liang
A1 Stuart G. Jarrett
A1 Manisha Patel
YR 2008
UL http://www.jneurosci.org/content/28/45/11550.abstract
AB Chelatable iron is an important catalyst for the initiation and propagation of free radical reactions and implicated in the pathogenesis of diverse neuronal disorders. Studies in our laboratory have shown that mitochondria are the principal source of reactive oxygen species production after status epilepticus (SE). We asked whether SE modulates mitochondrial iron levels by two independent methods and whether consequent mitochondrial dysfunction and neuronal injury could be ameliorated with a cell-permeable iron chelator. Kainate-induced SE resulted in a time-dependent increase in chelatable iron in mitochondrial but not cytosolic fractions of the rat hippocampus. Systemically administered N,N′-bis (2-hydroxybenzyl) ethylenediamine-N,N′-diacetic acid (HBED), a synthetic iron chelator, ameliorated SE-induced changes in chelatable iron, mitochondrial oxidative stress (8-hydroxy-2′ deoxyguanosine and glutathione depletion), mitochondrial DNA integrity and hippocampal cell loss. Measurement of brain HBED levels after systemic administration confirmed its penetration in hippocampal mitochondria. These results suggest a role for mitochondrial iron in the pathogenesis of SE-induced brain damage and subcellular iron chelation as a novel therapeutic approach for its management.