Lab Anim Res.  2017 Sep;33(3):202-208. 10.5625/lar.2017.33.3.202.

Hyperglycemia exacerbates downregulation of dynamin-like protein 1 in ischemic cerebral injury

Affiliations
  • 1Department of Anatomy, College of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, Jinju, Korea. pokoh@gnu.ac.kr
  • 2Division of Life Science and Applied Life Science, College of Natural Sciences, Gyeongsang National University, Jinju, Korea.

Abstract

Ischemic stroke is one of the leading causes of adult disability and death. Hyperglycemia is associated with an increased risk of stroke and poor outcomes after brain injury. Dynamin-like protein I (DLP-1) regulates mitochondrial fission and promotes mitochondrial dynamics. Neurodegenerative diseases are associated with mitochondrial dysfunction, and the downregulation of DLP-1 has been previously identified in a stroke animal model. Here, we investigated the changes in DLP-1 protein expression in an animal model of focal cerebral ischemia with induced hyperglycemia. Streptozotocin (40 mg/kg) was intraperitoneally injected into male rats to induce hyperglycemia, and middle cerebral artery occlusion (MCAO) was surgically induced 4 weeks after streptozotocin treatment. Brain tissue was isolated 24 hours after MCAO, and cerebral cortex samples were used for this study. Proteomics revealed a decrease in DLP-1 expression in MCAO animals when compared with controls, and this downregulation was more prominent in MCAO animals with hyperglycemia. Reverse-transcription polymerase chain reaction and Western blot analyses confirmed that DLP-1 was significantly downregulated in MCAO-injured animals with hyperglycemia compared to those without hyperglycemia. The decrease in DLP-1 indicates mitochondrial morphological changes and dysfunction. Together, these results suggest that the severe decrease of DLP-1 seen after brain injury under hyperglycemic conditions may exacerbate the damage to the brain.

Keyword

Brain ischemia; hyperglycemia; MCAO; dynamin-like protein 1

MeSH Terms

Adult
Animals
Blotting, Western
Brain
Brain Injuries
Brain Ischemia
Cerebral Cortex
Down-Regulation*
Humans
Hyperglycemia*
Infarction, Middle Cerebral Artery
Male
Mitochondrial Dynamics
Models, Animal
Neurodegenerative Diseases
Polymerase Chain Reaction
Proteomics
Rats
Streptozocin
Stroke
Streptozocin
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