title: Methylene blue protects the cortical blood-brain barrier against ischemia/reperfusion-induced disruptions.
abstract: OBJECTIVE
  To investigate the effects of cardiac arrest and the reperfusion syndrome on blood-brain barrier permeability and evaluate whether methylene blue counteracts blood-brain barrier disruption in a pig model of controlled cardiopulmonary resuscitation.
  
  
  METHODS
  Randomized, prospective, laboratory animal study.
  
  
  METHODS
  University-affiliated research laboratory.
  
  
  METHODS
  Forty-five piglets.
  
  
  METHODS
  Forty-five anesthetized piglets were subjected to cardiac arrest alone or 12-min cardiac arrest followed by 8 mins cardiopulmonary resuscitation. The first group (n = 16) was used to evaluate blood-brain barrier disruptions after untreated cerebral ischemia after 0, 15, or 30 mins after untreated cardiac arrest. The other two groups received either an infusion of saline (n = 10) or infusion of saline with methylene blue (n = 12) 1 min after the start of cardiopulmonary resuscitation and continued 50 mins after return of spontaneous circulation. In these groups, brains were removed for immunohistological analyses at 30, 60, and 180 mins after return of spontaneous circulation.
  
  
  RESULTS
  An increase of injured neurons and albumin immunoreactivity was demonstrated with increasing duration of ischemia/reperfusion. Less blood-brain barrier disruption was observed in subjects receiving methylene blue as demonstrated by decreased albumin leakage (p < .01), water content (p < .05), and neuronal injury (p < .01). Methylene blue treatment reduced cerebral tissue nitrite/nitrate content (p < .05) and the number of inducible and neuronal nitric oxide synthase-activated cortical cells during administration (p < .01). Meanwhile, the number of cortical endothelial nitric oxide synthase-activated cells increased over time (p < .001).
  
  
  CONCLUSIONS
  Cerebral tissue water content, blood-brain barrier permeability and neurologic injury were increased early in reperfusion after cardiac arrest. Methylene blue exerted neuroprotective effects against the brain damage associated with the ischemia/reperfusion injury and ameliorated the blood-brain barrier disruption by decreasing nitric oxide metabolites.
authors: Department of Surgical Sciences/Anaesthesiology and Critical Care Medicine, Uppsala University, Uppsala, Sweden. adriana.miclescu@akademiska.se
authors: Adriana
authors: A
authors: Miclescu
authors: Hari Shanker
authors: HS
authors: Sharma
authors: Cécile
authors: C
authors: Martijn
authors: Lars
authors: L
authors: Wiklund
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D015153:Blotting, Western; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D016887:Cardiopulmonary Resuscitation; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D006323:Heart Arrest / Q000150:complications; D008751:Methylene Blue / Q000494:pharmacology*; D009566:Nitrates / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D010100:Oxygen / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013552:Swine; D014882:Water-Electrolyte Balance
chemical_list: D009566:Nitrates; D009573:Nitrites; D019001:Nitric Oxide Synthase; D010100:Oxygen; D008751:Methylene Blue