Abstract
The effects of ischemia–reperfusion on opening of the mitochondrial permeability transition pore (mPTP) and its blockade in the immature brain are not fully understood. Presently, we evaluated the effect of cyclosporine A (CsA) on cell death and mPTP opening in a model of transient focal ischemia induced by permanent left middle cerebral artery, and homolateral transient common carotid artery occlusion (50min) in P7 rats. CsA (10mg/kg) was administered 14h before induction of ischemia and effects were analyzed at 30–40min and 48h after reperfusion. CsA administration reduced infarct size, DNA fragmentation and apoptotic bodies, and inflammatory responses in mild but not severe injury. CsA increased the Ca2+ load required to open the mPTP (78.4±19.2 vs. 50.2±19.9nmol.mg−1 protein, p<0.05) in limiting the decoupling of the respiratory chain by unchanged state 3 but reduced state 4, and attenuated early calpain-mediated alpha-spectrin proteolysis. In conclusion, CsA mediates inhibition of mPTP opening and has a tendency to protect immature rat brain against mild ischemic injury. This article is part of a Special Issue entitled "Interaction between repair, disease, & inflammation."
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