Hyperbaric Oxygen Reduces Infarction Volume and Hemorrhagic Transformation Through ATP/NAD+/Sirt1 Pathway in Hyperglycemic Middle Cerebral Artery Occlusion Rats

Qin Hu, Anatol Manaenko, Hetao Bian, Zongduo Guo, Jun Long Huang, Zhen Ni Guo, Peng Yang, Jiping Tang, John H. Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Purpose-Energy depletion is a critical factor leading to cell death and brain dysfunction after ischemic stroke. In this study, we investigated whether energy depletion is involved in hyperglycemia-induced hemorrhagic transformation after ischemic stroke and determined the pathway underlying the beneficial effects of hyperbaric oxygen (HBO). Methods-After 2-hour middle cerebral artery occlusion, hyperglycemia was induced by injecting 50% dextrose (6 mL/kg) intraperitoneally at the onset of reperfusion. Immediately after it, rats were exposed to HBO at 2 atmospheres absolutes for 1 hour. ATP synthase inhibitor oligomycin A, nicotinamide phosphoribosyl transferase inhibitor FK866, or silent mating type information regulation 2 homolog 1 siRNA was administrated for interventions. Infarct volume, hemorrhagic volume, and neurobehavioral deficits were recorded; the level of blood glucose, ATP, and nicotinamide adenine dinucleotide and the activity of nicotinamide phosphoribosyl transferase were monitored; the expression of silent mating type information regulation 2 homolog 1, acetylated p53, acetylated nuclear factor-κB, and cleaved caspase 3 were detected by Western blots; and the activity of matrix metalloproteinase-9 was assayed by zymography. Results-Hyperglycemia deteriorated energy metabolism and reduced the level of ATP and nicotinamide adenine dinucleotide and exaggerated hemorrhagic transformation, blood-brain barrier disruption, and neurological deficits after middle cerebral artery occlusion. HBO treatment increased the levels of the ATP and nicotinamide adenine dinucleotide and consequently increased silent mating type information regulation 2 homolog 1, resulting in attenuation of hemorrhagic transformation, brain infarction, as well as improvement of neurological function in hyperglycemic middle cerebral artery occlusion rats. Conclusions-HBO induced activation of ATP/nicotinamide adenine dinucleotide/silent mating type information regulation 2 homolog 1 pathway and protected blood-brain barrier in hyperglycemic middle cerebral artery occlusion rats. HBO might be promising approach for treatment of acute ischemic stroke patients, especially patients with diabetes mellitus or treated with r-TPA (recombinant tissue-Type plasminogen activator).

Original languageEnglish
Pages (from-to)1655-1664
Number of pages10
JournalStroke
Volume48
Issue number6
DOIs
StatePublished - Jun 1 2017

ASJC Scopus Subject Areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Keywords

  • NAD
  • NAMPT
  • Sirt1 and hemorrhagic transformation
  • hyperbaric oxygenation
  • stroke
  • Hyperbaric Oxygenation/methods
  • Signal Transduction
  • Nicotinamide Phosphoribosyltransferase/metabolism
  • Adenosine Triphosphate/metabolism
  • Rats
  • Male
  • Rats, Sprague-Dawley
  • Cerebral Hemorrhage/complications
  • Brain Ischemia/metabolism
  • Animals
  • Sirtuin 1/metabolism
  • Hyperglycemia/complications
  • Stroke/metabolism
  • Infarction, Middle Cerebral Artery/metabolism
  • Disease Models, Animal
  • NAD/metabolism

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