Methylene blue protects the cortical blood-brain barrier against ischemia/reperfusion-induced disruptions

• Published in: Critical care medicine Vol. 38; no. 11; p. 2199
• Main Authors: Miclescu, Adriana, Sharma, Hari Shanker, Martijn, Cécile, Wiklund, Lars
• Format: Journal Article
• Language: English
• Published: United States 01.11.2010
• Subjects: Animals; Blood-Brain Barrier - drug effects; Blotting, Western; Brain Ischemia - etiology; Brain Ischemia - metabolism; Brain Ischemia - physiopathology; Cardiopulmonary Resuscitation; Cerebral Cortex - chemistry; Cerebral Cortex - metabolism; Heart Arrest - complications; Methylene Blue - pharmacology; Nitrates - analysis; Nitric Oxide Synthase - drug effects; Nitric Oxide Synthase - metabolism; Nitrites - analysis; Oxygen - metabolism; Reperfusion Injury - metabolism; Reperfusion Injury - physiopathology; Reperfusion Injury - prevention & control; Swine; Water-Electrolyte Balance
• ISSN: 1530-0293
• DOI: 10.1097/CCM.0b013e3181f26b0c

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. Randomized, prospective, laboratory animal study. University-affiliated research laboratory. Forty-five piglets. 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. 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). 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.