Cyclosporine A attenuates hypoxic–ischemic brain injury in newborn rats

Abstract

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 2 h of 8% oxygen following a unilateral carotid artery ligation. With a single dose of CsA treatment (20 mg/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.