Hyperbaric oxygen preconditioning attenuates hemorrhagic transformation through reactive oxygen species/thioredoxin-interacting protein/nod-like receptor protein 3 pathway in hyperglycemic middle cerebral artery occlusion rats

Zhen Ni Guo, Liang Xu, Qin Hu, Nathanael Matei, Peng Yang, Lu Sha Tong, Yue He, Zongduo Guo, Jiping Tang, Yi Yang, John H. Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: To clarify whether hyperbaric oxygen preconditioning can attenuate hyperglycemia-enhanced hemorrhagic transformation and to establish a role for Nod-like receptor protein 3 inflammasome in the pathophysiology of hemorrhagic transformation. Design: Controlled prospective animal study. Setting: University research laboratory. Subjects: Male Sprague-Dawley rats weighing 260-280 g. Interventions: Rats received 1-hour-long hyperbaric oxygen preconditioning for five consecutive days. Hyperglycemic middle cerebral artery occlusion model was induced at 24 hours after the last hyperbaric oxygen exposure. Reactive oxygen species scavenger (N-acetyl-l-cysteine), thioredoxin-interacting protein small interfering RNA, and Nod-like receptor protein 3 small interfering RNA were given in different groups separately to verify the possible pathway. Measurements and Main Results: Rats were randomly divided into sham, middle cerebral artery occlusion, middle cerebral artery occlusion + dextrose, middle cerebral artery occlusion + dextrose + normobaric oxygen preconditioning, middle cerebral artery occlusion + dextrose + hyperbaric oxygen, middle cerebral artery occlusion + dextrose + hyperbaric oxygen + N-acetyl-l-cysteine, middle cerebral artery occlusion + dextrose + hyperbaric oxygen + control small interfering RNA, middle cerebral artery occlusion + dextrose + hyperbaric oxygen + thioredoxin-interacting protein small interfering RNA, and middle cerebral artery occlusion + dextrose + hyperbaric oxygen + Nod-like receptor protein 3 small interfering RNA groups. Hyperglycemia was induced by administration of 50% dextrose (6 mL/kg) intraperitoneally 30 minutes before middle cerebral artery occlusion. Control small interfering RNA/thioredoxin-interacting protein small interfering RNA or Nod-like receptor protein 3 small interfering RNA (500 pmol/5 μL) were injected intracerebroventricularly 72 hours before middle cerebral artery occlusion for intervention. The neurologic scores, infarction and hemorrhage volumes, the expression of Nod-like receptor protein 3, and its downstream targets were analyzed. Hyperbaric oxygen preconditioning decreased both infarction and hemorrhage volumes and improved neurobehavioral function. In addition, hyperbaric oxygen preconditioning provided additional protective effects in hemorrhagic transformation, which was independent of infarction volume. The benefits of hyperbaric oxygen preconditioning on hyperglycemic middle cerebral artery occlusion rats were reversed after blocking the reactive oxygen species/thioredoxin-interacting protein/Nod-like receptor protein 3 pathway. Conclusions: Nod-like receptor protein 3 inflammasome played an important role in hyperglycemia-enhanced hemorrhagic transformation. Hyperbaric oxygen preconditioning attenuated hemorrhagic transformation through reactive oxygen species/thioredoxin-interacting protein/Nod-like receptor protein 3 pathway.

Original languageEnglish
Pages (from-to)e403-e411
JournalCritical Care Medicine
Volume44
Issue number6
DOIs
StatePublished - Jun 1 2016

ASJC Scopus Subject Areas

  • Critical Care and Intensive Care Medicine

Keywords

  • Nod-like receptor protein 3
  • hemorrhagic transformation
  • hyperbaric oxygen preconditioning
  • middle cerebral artery occlusion
  • thioredoxin-interacting protein
  • Prospective Studies
  • Male
  • Receptors, Cell Surface
  • Glucose
  • Middle Cerebral Artery
  • Brain Infarction/etiology
  • Arterial Occlusive Diseases/complications
  • Cerebral Hemorrhage/etiology
  • Inflammasomes/metabolism
  • Reactive Oxygen Species/metabolism
  • Matrix Metalloproteinase 9/metabolism
  • Hyperglycemia/chemically induced
  • Signal Transduction/genetics
  • Rats
  • Rats, Sprague-Dawley
  • Animals
  • Carrier Proteins/genetics
  • Acetylcysteine/metabolism
  • RNA, Small Interfering
  • Cell Cycle Proteins
  • Hyperbaric Oxygenation

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