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Regulation of Neuron Death in Neonatal Hypoxia‐Ischemia
Author(s) -
Shacka John J,
DeWitte Cary,
Roth Kevin A,
Ness Jayne M
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.235.6
Subject(s) - neun , western blot , programmed cell death , apoptosis , neuron , hypoxia (environmental) , autophagy , ischemia , hippocampus , biology , microbiology and biotechnology , medicine , endocrinology , neuroscience , chemistry , immunohistochemistry , biochemistry , organic chemistry , oxygen , gene
Hypoxia ischemia (HI) is a major cause of neonatal brain injury and often results in long‐term neurological disability. We have shown that the pro‐apoptotic molecules such as Bax critically regulate neuronal injury following HI. Alterations in the autophagy‐lysosome pathway (ALP) are known to regulate neuron death following neonatal HI and our goal is to delineate mechanisms by which ALP regulates neuron death following neonatal HI. Postnatal day 7 B57BL6/J mice underwent unilateral carotid ligation followed by 45 min exposure to 8% oxygen, and were euthanized 3‐48h later. Brain samples were processed either for IHC or western blot analysis. Within 12h after neonatal HI, intense cytosolic CD immunoreactivity was observed in the ipsilateral hippocampus and peaked at 24‐48h, suggesting induction of lysosomal membrane permeabilization. Increased CD levels were confirmed by western blot analysis. Cytosolic CD co‐localized with NeuN and cleaved caspase‐3 but not p53 in the ipsilateral hippocampus. Bax deficiency attenuated cleaved caspase‐3 immunoreactivity but this attenuation was incomplete, suggesting an additional role for the extrinsic apoptotic pathway in neonatal HI. These results suggest the existence of multiple neuron death pathways following neonatal HI and studies are ongoing to determine if these pathways are regulated through alterations in the ALP.