Department of Pediatrics, Ilsan Paik Hospital, College of Medicine, Inje University, Ilsan, Republic of Korea.
Brain Res. 2010 Nov 4;1359:208-15. doi: 10.1016/j.brainres.2010.08.047. Epub 2010 Aug 22.
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.
环孢素 A（CsA）在成年动物的缺血性脑损伤中具有神经保护作用，因为它可以阻断线粒体膜的通透性转换。在这项研究中，我们研究了 CsA 对新生大鼠缺氧缺血（HI）诱导的脑损伤的神经保护作用。将 7 日龄 Sprague-Dawley 幼鼠置于 8%氧气中 2 小时，随后进行单侧颈总动脉结扎。在 HI 后立即给予 CsA（20mg/kg，腹腔内）单次剂量治疗，可明显减轻 HI 诱导的脑线粒体膜电位降低（用 5,5',6,6'-四氯-1,1',3,3'-四乙基苯并咪唑基-碳氰化碘化物[JC-1]测量）、三磷酸腺苷水平降低，以及脑乳酸水平升高，用 Annexin V 和碘化丙啶（V-PI）测量的凋亡和坏死细胞，以及用 2,3,5-三苯基氯化四唑（TTC）测量的梗死面积，在 48 小时时明显减轻，并且在 HI 后 2 周时，减少的脑体积也明显改善。综上所述，线粒体通透性转换抑制剂环孢素 A 可显著减轻缺氧缺血引起的线粒体膜电位降低、脑能量状态降低、凋亡和坏死细胞增加以及随之而来的未成熟脑梗死。
