Humanin prevents brain mitochondrial dysfunction in a cardiac ischaemia-reperfusion injury model.

What is the central question of this study? Myocardial ischaemia-reperfusion (I/R) injury causes interference in the systemic circulation and damages not only the heart but also several vital organs, including the brain. Recently, a novel peptide called humanin has been shown to exert potent neuroprotective effects. However, the effect of humanin on the brain during cardiac I/R injury has not yet been investigated. What is the main finding and its importance? The I/R injury caused blood-brain barrier breakdown, increased brain oxidative stress and resulted in mitochondrial dysfunction. Only the humanin treatment before ischaemia attenuated brain mitochondrial dysfunction, but it did not prevent blood-brain barrier breakdown or brain oxidative stress. Humanin treatment during ischaemia and in the reperfusion period provided no neuroprotection. These findings indicate that humanin exerted neuroprotection during cardiac I/R injury via improved brain mitochondrial function. Myocardial ischaemia-reperfusion (I/R) injury causes interference in the systemic circulation and damages not only the heart but also several vital organs, including the brain. Nevertheless, limited information is available regarding the effect of cardiac I/R injury on the brain, including blood-brain barrier (BBB) breakdown, brain oxidative stress and mitochondrial function. Recently, a novel peptide called humanin has been shown to exert potent neuroprotective effects. However, the effect of humanin on the brain during cardiac I/R injury has not yet been investigated. Forty-two male Wistar rats were divided into the following two groups: an I/R group, which was subjected to a 30 min left anterior descending coronary artery occlusion followed by 120 min reperfusion (I/R group; n = 36); and a sham group (n = 6). The I/R group was divided into six subgroups. Each subgroup was given either vehicle or humanin analogue (84 μg kg(-1) , i.v.) at three different time points, namely before ischaemia, during ischaemia or at the onset of reperfusion. At the end of the experimental protocol, animals were killed and the brains removed for determination of mitochondrial function, oxidative stress and Western blot analyses. The I/R injury caused BBB breakdown, increased brain oxidative stress and resulted in mitochondrial dysfunction. Only the humanin treatment before ischaemia attenuated brain mitochondrial dysfunction, but it did not prevent BBB breakdown or brain oxidative stress. Humanin treatment during ischaemia and in the reperfusion period provided no neuroprotection. These findings indicate that humanin exerted neuroprotection during cardiac I/R injury via improved brain mitochondrial function.