Document Detail


Methylene blue protects the cortical blood-brain barrier against ischemia/reperfusion-induced disruptions.
MedLine Citation:
PMID:  20711066     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: 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. DESIGN: Randomized, prospective, laboratory animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Forty-five piglets. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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). CONCLUSION: 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:
Adriana Miclescu; Hari Shanker Sharma; Cécile Martijn; Lars Wiklund
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  38     ISSN:  1530-0293     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-20     Completed Date:  2010-11-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2199-206     Citation Subset:  AIM; IM    
Affiliation:
Department of Surgical Sciences/Anaesthesiology and Critical Care Medicine, Uppsala University, Uppsala, Sweden. adriana.miclescu@akademiska.se
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood-Brain Barrier / drug effects*
Blotting, Western
Brain Ischemia / etiology,  metabolism,  physiopathology*
Cardiopulmonary Resuscitation
Cerebral Cortex / chemistry,  metabolism
Heart Arrest / complications
Methylene Blue / pharmacology*
Nitrates / analysis
Nitric Oxide Synthase / drug effects,  metabolism
Nitrites / analysis
Oxygen / metabolism
Reperfusion Injury / metabolism,  physiopathology,  prevention & control*
Swine
Water-Electrolyte Balance
Chemical
Reg. No./Substance:
0/Nitrates; 0/Nitrites; 61-73-4/Methylene Blue; 7782-44-7/Oxygen; EC 1.14.13.39/Nitric Oxide Synthase
Comments/Corrections
Comment In:
Crit Care Med. 2010 Nov;38(11):2265-6   [PMID:  20959759 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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