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CNS Neurosci Ther. 2012 Mar;18(3):250-60. doi: 10.1111/j.1755-5949.2012.00295.x.

Excessive autophagy contributes to neuron death in cerebral ischemia.

Author information

1
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada.

Abstract

AIMS:

To determine the extent to which autophagy contributes to neuronal death in cerebral hypoxia and ischemia.

METHODS:

We performed immunocytochemistry, western blot, cell viability assay, and electron microscopy to analyze autophagy activities in vitro and in vivo.

RESULTS:

In both primary cortical neurons and SH-SY5Y cells exposed to oxygen and glucose deprivation (OGD)for 6 h and reperfusion (RP) for 24, 48, and 72 h, respectively, an increase of autophagy was observed as determined by the increased ratio of LC3-II to LC3-I and Beclin-1 (BECN1) expression. Using Fluoro-Jade C and monodansylcadaverine double-staining, and electron microscopy we found the increment in autophagy after OGD/RP was accompanied by increased autophagic cell death, and this increased cell death was inhibited by the specific autophagy inhibitor, 3-methyladenine. The presence of large autolysosomes and numerous autophagosomes in cortical neurons were confirmed by electron microscopy. Autophagy activities were increased dramatically in the ischemic brains 3-7 days postinjury from a rat model of neonatal cerebral hypoxia/ischemia as shown by increased punctate LC3 staining and BECN1 expression.

CONCLUSION:

Excessive activation of autophagy contributes to neuronal death in cerebral ischemia.

[Indexed for MEDLINE]

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