Humanin Exerts Neuroprotection During Cardiac Ischemia-Reperfusion Injury

Cardiac ischemia-reperfusion (I/R) injury has been shown to impair brain function. Humanin analogue (HNG) given prior to cardiac ischemia has been shown to attenuate both heart and brain mitochondrial dysfunction caused by cardiac I/R injury. In a clinical setting, patients received medical treatment for acute myocardial infarction either during or after the onset of myocardial ischemia; thus, in this study, we tested the hypothesis that the administration of HNG during cardiac I/R injury has therapeutic potential for brain protection. Thirty-six male Wistar rats were divided into two groups: a cardiac I/R group (n = 30), and a sham group (n = 6). The I/R rats were then divided into five subgroups to receive: 1) vehicle; 2) HNG (84 mu g/kg); 3) HNG (168 mu g/kg); 4) HNG (252 mu g/kg) intravenously administered during the cardiac-ischemia; and 5) HNG at 252 mu g/kg given at the onset of reperfusion. At the end of treatment, brains were removed for determination of blood-brain barrier (BBB) breakdown, oxidative stress, brain mitochondrial function, brain mitochondrial dynamics, p-tau, amyloid-beta (A beta) and apoptosis. HNG at a dose of 168 and 252 mu g/kg administered during ischemia, and 252 mu g/kg given at the onset of reperfusion effectively attenuated the brain mitochondrial dysfunction, tau hyperphosphorylation and A beta accumulation, and apoptosis, without reducing BBB breakdown, brain oxidative stress, or mitochondrial dynamic, caused by cardiac I/R injury. In conclusion, humanin exerted neuroprotection during induced cardiac I/R injury via improvement in brain mitochondrial function, and the reduction of Alzheimer's disease pathology and apoptosis.