title: 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 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.
authors.affiliation: Department of Pediatrics, Ilsan Paik Hospital, College of Medicine, Inje University, Ilsan, Republic of Korea.
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Hwang
authors.forename: Jang Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyung-Hoon
authors.initials: KH
authors.lastname: Lee
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Bae
authors.forename: Dong Kyung
authors.initials: DK
authors.lastname: Sung
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Chang
authors.forename: Won Soon
authors.initials: WS
authors.lastname: Park
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D002469:Cell Separation; D016572:Cyclosporine / Q000494:pharmacology*; D005434:Flow Cytometry; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D016572:Cyclosporine