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Methylene blue protects the cortical blood-brain barrier against ischemia/reperfusion-induced disruptions
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. (cardiopulmonary resuscitation)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
2010 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 38, no 11, 2199-2206 p.Article in journal (Refereed) Published
Abstract [en]

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 in-creasing 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. (Crit Care Med 2010; 38: 2199-2206)

Place, publisher, year, edition, pages
2010. Vol. 38, no 11, 2199-2206 p.
Keyword [en]
cardiac arrest (CA), cardiopulmonary resuscitation (CPR), blood-brain barrier (BBB), methylene blue (MB), nitric oxide (NO), nitrite/nitrate content, nitric oxide synthase (NOS)
National Category
Anesthesiology and Intensive Care Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-133822DOI: 10.1097/CCM.0b013e3181f26b0cISI: 000283235400016OAI: oai:DiVA.org:uu-133822DiVA: diva2:371320
Available from: 2010-11-19 Created: 2010-11-16 Last updated: 2015-06-09Bibliographically approved

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Miclescu, AdrianaSharma, Hari ShankerMartijn, CécileWiklund, Lars

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