title: Pentoxifylline Alleviates Perinatal Hypoxic-Ischemia-Induced Short-term Memory Impairment by Suppressing Apoptosis in the Hippocampus of Rat Pups.
abstract: OBJECTIVE
  Perinatal hypoxic-ischemic brain damage is a major cause of acute mortality and chronic neurologic morbidity in infants and children. We investigated the effects of pentoxifylline, a methylxanthine derivative and type-4 phosphodiesterase inhibitor, on short-term memory and apoptotic neuronal cell death in the hippocampus following perinatal hypoxic-ischemia in newborn rats.
  
  
  METHODS
  We used a step-down avoidance task to evaluate short-term memory and 3ʹ-5ʹ-cyclic adenosine monophosphate (cAMP) assay to detect cAMP levels. We evaluated apoptosis using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay for evidence of DNA fragmentation, immunohistochemistry for caspase-3 levels, and western blot for Bcl-2 and Bax.
  
  
  RESULTS
  Perinatal hypoxic-ischemic injury increased apoptotic cell death in the hippocampus, resulting in impaired short-term memory with decreased cAMP levels. Pentoxifylline treatment improved short-term memory by suppressing apoptotic cell death in the hippocampus with elevated cAMP levels.
  
  
  CONCLUSIONS
  Pentoxifylline ameliorated perinatal hypoxic-ischemia in rat pups. This alleviating effect could be ascribed to the inhibition apoptosis due to increased cAMP production by pentoxifylline.
authors.affiliation: Department of Surgery, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon, Korea.
authors.forename: Je Hoon
authors.identifier: 0000-0002-6930-3793
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Sung Eun
authors.identifier: 0000-0003-3742-0271
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Jun Jang
authors.identifier: 0000-0001-5594-5915
authors.initials: JJ
authors.lastname: Jin
authors.affiliation: Department of Emergency Medicine, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Han Sung
authors.identifier: 0000-0001-7477-5405
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Chang Ju
authors.identifier: 0000-0003-4749-5795
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Il Gyu
authors.identifier: 0000-0003-2696-6869
authors.initials: IG
authors.lastname: Ko
keywords: Apoptosis; Cyclic AMP; Hypoxia-Ischemia; Memory; Pentoxifylline; Phosphodiesterase-4 Inhibitors