Hyperbaric oxygen preconditioning attenuates hyperglycemia-enhanced hemorrhagic transformation by inhibiting matrix metalloproteinases in focal cerebral ischemia in rats

Yoshiteru Soejima, Qin Hu, Paul R. Krafft, Mutsumi Fujii, Jiping Tang, John H. Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Hyperglycemia dramatically aggravates brain infarct and hemorrhagic transformation (HT) after ischemic stroke. Oxidative stress and matrix metalloproteinases (MMPs) play an important role in the pathophysiology of HT. Hyperbaric oxygen preconditioning (HBO-PC) has been proved to decrease oxidative stress and has been demonstrated to be neuroprotective in experimental stroke models. The present study determined whether HBO-PC would ameliorate HT by a pre-ischemic increase of reactive oxygen species (ROS) generation, and a suppression of MMP-2 and MMP-9 in hyperglycemic middle cerebral artery occlusion (MCAO) rats. Rats were pretreated with HBO (100% O2, 2.5atmosphere absolutes) 1h daily for 5days before MCAO. Acute hyperglycemia was induced by an injection of 50% dextrose. Neurological deficits, infarction volume and hemorrhagic volume were assessed 24h and 7days after ischemia. ROS scavenger n-acetyl cysteine (NAC), hypoxia-inducible factor-1α (HIF-1α), inhibitor 2-methoxyestradiol (2ME2) and activator cobalt chloride (CoCl2), and MMP inhibitor SB-3CT were administrated for mechanism study. The activity of MMP-2 and MMP-9, and the expression HIF-1α were measured. HBO-PC improved neurological deficits, and reduced hemorrhagic volume; the expression of HIF-1α was significantly decreased, and the activity of MMP-2 and MMP-9 was reduced by HBO-PC compared with vehicle group. Our results suggested that HBO-PC attenuated HT via decreasing HIF-1α and its downstream MMP-2 and MMP-9 in hyperglycemic MCAO rats. © 2013 Elsevier Inc.
Original languageEnglish
Pages (from-to)737-743
Number of pages7
JournalExperimental Neurology
Volume247
DOIs
StatePublished - Sep 2013

ASJC Scopus Subject Areas

  • Neurology
  • Developmental Neuroscience

Keywords

  • Hemorrhagic transformation
  • Hyperbaric oxygen preconditioning
  • MCAO
  • MMP-2 and MMP-9
  • Infarction, Middle Cerebral Artery/complications
  • Male
  • Glucose/toxicity
  • Metalloproteases/metabolism
  • Time Factors
  • Cerebral Hemorrhage/etiology
  • Cobalt/pharmacology
  • Hemoglobins/metabolism
  • Cerebral Infarction/etiology
  • Gene Expression Regulation/drug effects
  • Disease Models, Animal
  • Ischemic Preconditioning/methods
  • Reactive Oxygen Species/metabolism
  • Hyperbaric Oxygenation/methods
  • Hyperglycemia/chemically induced
  • Rats
  • Blood Glucose
  • Free Radical Scavengers/therapeutic use
  • Rats, Sprague-Dawley
  • Animals
  • Neurologic Examination
  • Analysis of Variance
  • Spectrophotometry

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