Cyclosporine A (CsA) is neuroprotective in ischemic brain injuries of adult animals because it blocks the permeability transition of the mitochondrial membrane. In this study, we examined the neuroprotective effect of CsA on hypoxia-ischemia (HI)-induced brain injury in newborn rats. Seven-day-old Sprague-Dawley rat pups were subjected to 2h of 8% oxygen following a unilateral carotid artery ligation. With a single dose of CsA treatment (20mg/kg, intraperitoneal) given immediately after HI, the HI-induced decrease in brain mitochondrial membrane potential measured with 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) and adenosine triphosphate levels, and increase in the brain lactate level, both apoptotic and necrotic cells measured with annexin V and propidium iodide (V-PI), and infarct area measured with 2,3,5-triphenyltetrazolium chloride (TTC) were significantly attenuated at 48 h, and the reduced brain volume also significantly improved 2 weeks following HI. In summary, Cyclosporine A, a mitochondrial permeability transition blocker, significantly attenuated hypoxia-ischemia-induced lowering of the mitochondrial membrane potential, cerebral energy status, increased apoptotic and necrotic cells, and the ensuing cerebral infarction in the immature brain.
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