benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and Hypoxia-Ischemia--Brain

The aim of this study was to determine whether hypoxic-ischemia from asphyxial cardiac arrest activates brain caspases-1 and -3, and the anti-apoptotic protein, XIAP. Asphyxial cardiac arrest in rats was used to induce hypoxic-ischemia. A pan-caspase inhibitor (zVAD) was given in the treatment group. At 72 h after reperfusion, caspase-3 and XIAP expression were present in multiple vulnerable brain regions, whereas caspase-1 was predominantly found in the CA1 hippocampus. zVAD significantly reduced expression of caspases and XIAP and the number of ischemic neurons in the CA1 hippocampus while neurological deficit scores were improved. We conclude that hypoxic-ischemia increases caspases-1 and-3, and XIAP expression. Treatment with zVAD significantly decreases caspase and XIAP expression in these brain regions and improves neurological outcome.

Topics: Amino Acid Chloromethyl Ketones; Animals; Asphyxia; Brain; Caspase 1; Caspase 3; Caspase Inhibitors; Caspases; Cell Death; Cysteine Proteinase Inhibitors; Down-Regulation; Gene Expression Regulation, Enzymologic; Heart Arrest; Hippocampus; Hypoxia-Ischemia, Brain; Immunohistochemistry; Male; Neurons; Proteins; Rats; Rats, Sprague-Dawley; X-Linked Inhibitor of Apoptosis Protein