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CNS Neurosci Ther. 2013 Oct;19(10):753-63. doi: 10.1111/cns.12123. Epub 2013 Jun 3.

The involvement of autophagy pathway in exaggerated ischemic brain damage in diabetic mice.

Author information

1
Department of Neurology, Nanjing University School of Medicine, Jinling Hospital, Nanjing, China; Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA.

Abstract

BACKGROUND:

Patients with Diabetes are at greater risk for ischemic stroke and usually suffer more severe ischemic brain damage than nondiabetic patients. However, the underlying mechanism of the exaggerated injury is not well defined.

AIMS:

Macroautophagy (hereafter called autophagy in this report) plays a key role in cellular homeostasis and may contribute to cell death as well. Our aim was to determine whether autophagy was involved in the enhanced susceptibility of diabetic brain cells to ischemic injury and explore it as a possible target for the treatment of stroke in a diabetic condition.

RESULTS:

A type II diabetic mouse model generated by combined administration of streptozotocin and nicotinamide showed enlarged infarct volume, increased cell death and excessive blood-brain barrier (BBB) disruption compared with nondiabetic stroke mice. After ischemic stroke, both diabetic and nondiabetic mice showed enhanced autophagosome formation and autophagic flux as demonstrated by increased expression of autophagy signals Beclin 1, microtubule-associated protein light-chain II (LC3-II), and decreased autophagy-specific substrate p62. The increased autophagic activity was significantly higher in diabetic stroke mice than that in nondiabetic stroke mice. The autophagy inhibitor 3-methyladenine (3-MA) attenuated the exaggerated brain injury and improved functional recovery.

CONCLUSIONS:

These data suggest that autophagy contributes to exacerbated brain injury in diabetic condition, and autophagy-mediated cell death may be a therapeutic target in diabetic stroke.

KEYWORDS:

Autophagy; Blood-brain barrier; Cell death; Diabetes; Ischemic stroke

PMID:
23731488
DOI:
10.1111/cns.12123
[Indexed for MEDLINE]
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