Cyclosporine A attenuates hypoxic-ischemic brain injury in newborn rats.
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.
Hwang
Jong Hee
JH
Department of Pediatrics, Ilsan Paik Hospital, College of Medicine, Inje University, Ilsan, Republic of Korea.
Lee
Jang Hoon
JH
Lee
Kyung-Hoon
KH
Bae
Eun Joo
EJ
Sung
Dong Kyung
DK
Chang
Yun Sil
YS
Park
Won Soon
WS
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
D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D016572:Cyclosporine