OBJECTIVE: Delayed preconditioning genetically reprograms the response to ischemic injury. Subclinical bacterial lipopolysaccharide acts through preconditioning, powerfully protecting against experimental stroke. We investigated the potential for lipopolysaccharide to protect against brain injury related to cardiopulmonary bypass. METHODS: Neonatal piglets were blindly and randomly preconditioned with lipopolysaccharide (n = 6) or saline (n = 6). Three days later, they experienced 2 hours of deep hypothermic circulatory arrest before being weaned and supported anesthetized for 20 hours in an intensive care setting. Controls included cardiopulmonary bypass without deep hypothermic circulatory arrest (n = 3) and no cardiopulmonary bypass (n = 3). Brain injury was quantified by light and fluorescent microscopy (Fluoro-Jade; Histo-Chem, Inc, Jefferson, Ark). RESULTS: All animals were clinically indistinguishable before surgery. Perioperative and postoperative parameters between experimental groups were similar. No control animal scored falsely positive. Histologic scores were 0.33 +/- 0.21, 0.66 +/- 0.42, and 0.5 +/- 0.24 in the cortex, basal ganglia, and hippocampus, respectively, in the lipopolysaccharide-treated animals but significantly worse in all saline control animals (1.33 +/- 0.21, P < .01; 1.66 +/- 0.33, P = .09; and 6.0 +/- 1.5, P < .01). One lipopolysaccharide-treated brain was histologically indistinguishable from controls. CONCLUSION: This is the first evidence that lipopolysaccharide can precondition against cardiopulmonary bypass-related injury. Because lipopolysaccharide preconditioning is a systemic phenomenon offering proven protection against myocardial, hepatic, and pulmonary injury, this technique offers enormous potential for protecting against systemic neonatal injury related to cardiopulmonary bypass.
OBJECTIVE: Delayed preconditioning genetically reprograms the response to ischemic injury. Subclinical bacterial lipopolysaccharide acts through preconditioning, powerfully protecting against experimental stroke. We investigated the potential for lipopolysaccharide to protect against brain injury related to cardiopulmonary bypass. METHODS: Neonatal piglets were blindly and randomly preconditioned with lipopolysaccharide (n = 6) or saline (n = 6). Three days later, they experienced 2 hours of deep hypothermic circulatory arrest before being weaned and supported anesthetized for 20 hours in an intensive care setting. Controls included cardiopulmonary bypass without deep hypothermic circulatory arrest (n = 3) and no cardiopulmonary bypass (n = 3). Brain injury was quantified by light and fluorescent microscopy (Fluoro-Jade; Histo-Chem, Inc, Jefferson, Ark). RESULTS: All animals were clinically indistinguishable before surgery. Perioperative and postoperative parameters between experimental groups were similar. No control animal scored falsely positive. Histologic scores were 0.33 +/- 0.21, 0.66 +/- 0.42, and 0.5 +/- 0.24 in the cortex, basal ganglia, and hippocampus, respectively, in the lipopolysaccharide-treated animals but significantly worse in all saline control animals (1.33 +/- 0.21, P < .01; 1.66 +/- 0.33, P = .09; and 6.0 +/- 1.5, P < .01). One lipopolysaccharide-treated brain was histologically indistinguishable from controls. CONCLUSION: This is the first evidence that lipopolysaccharide can precondition against cardiopulmonary bypass-related injury. Because lipopolysaccharide preconditioning is a systemic phenomenon offering proven protection against myocardial, hepatic, and pulmonary injury, this technique offers enormous potential for protecting against systemic neonatal injury related to cardiopulmonary bypass.
Authors: Philberta Y Leung; Susan L Stevens; Amy E B Packard; Nikola S Lessov; Tao Yang; Valerie K Conrad; Noortje N A M van den Dungen; Roger P Simon; Mary P Stenzel-Poore Journal: Stroke Date: 2012-03-08 Impact factor: 7.914
Authors: Frances Rena Bahjat; Rebecca L Williams-Karnesky; Steven G Kohama; G Alexander West; Kristian P Doyle; Maxwell D Spector; Theodore R Hobbs; Mary P Stenzel-Poore Journal: J Cereb Blood Flow Metab Date: 2011-02-02 Impact factor: 6.200
Authors: Susan L Stevens; Philberta Y Leung; Keri B Vartanian; Banu Gopalan; Tao Yang; Roger P Simon; Mary P Stenzel-Poore Journal: J Neurosci Date: 2011-06-08 Impact factor: 6.167