title: Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.
abstract: Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase.
authors.affiliation: aDepartment of Pediatrics, Xiangya Hospital, Central South University bDepartment of Pediatrics, Maternal and Child Health Hospital of Hunan Province, Changsha, Hunan Province, China.
authors.forename: Kaiwei
authors.initials: K
authors.lastname: Peng
authors.forename: Danfeng
authors.initials: D
authors.lastname: Tan
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Dandan
authors.initials: D
authors.lastname: Guo
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Chentao
authors.initials: C
authors.lastname: Liu
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004077:Digoxin / Q000008:administration & dosage*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000517:prevention & control*; D019194:Ischemic Preconditioning; D064231:Nestin / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: C577486:Nes protein, rat; D064231:Nestin; D018696:Neuroprotective Agents; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase