Evaluation of cyclosporine A in a stroke model in the immature rat brain. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Experimental Neurology Année : 2010

Evaluation of cyclosporine A in a stroke model in the immature rat brain.

Résumé

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 Ca(2+) 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.

Domaines

Neurosciences

Dates et versions

hal-00516644 , version 1 (10-09-2010)

Identifiants

Citer

Pierre-Louis Leger, Damien de Paulis, Sonia Branco, Philippe Bonnin, Elisabeth Couture-Lepetit, et al.. Evaluation of cyclosporine A in a stroke model in the immature rat brain.. Experimental Neurology, 2010, 230 (1), pp.58-66. ⟨10.1016/j.expneurol.2010.06.009⟩. ⟨hal-00516644⟩
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