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Author Notes:

Ling Wei, M.D., Department of Anesthesiology, Emory University School of Medicine, Atlanta, 101 Woodruff Circle, Suite 630, GA 30322, USA. Tel.: +1‐404‐718‐8661; Fax: +1‐404‐717‐6300; E‐mail: lwei7@emory.edu

Xinfeng Liu, M.D., Ph.D., Department of Neurology, Nanjing University School of Medicine, Jinling Hospital, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China. Tel.: +86‐25‐8537‐2631; Fax: +86‐25‐8480‐1861; E‐mail: xfliu2@gmail.com

The authors declare no conflict of interest.


Research Funding:

This work was supported by NIH grants NS057255 (LW), NS075338 (LW), NS062097 (LW), NS0458710 (SPY), and an AHA Established Investigator Award (LW).

This work was also supported by the NIH grant C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Pharmacology & Pharmacy
  • Neurosciences & Neurology
  • Autophagy
  • Blood-brain barrier
  • Cell death
  • Diabetes
  • Ischemic stroke
  • RATS
  • LC3

The Involvement of Autophagy Pathway in Exaggerated Ischemic Brain Damage in Diabetic Mice


Journal Title:

CNS Neuroscience and Therapeutics


Volume 19, Number 10


, Pages 753-763

Type of Work:

Article | Final Publisher PDF


Summary: 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.

Copyright information:

© 2013 John Wiley & Sons Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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