Pentoxifylline Alleviates Perinatal Hypoxic-Ischemia-Induced Short-term Memory Impairment by Suppressing Apoptosis in the Hippocampus of Rat Pups.

Je Hoon PARK; Sung Eun KIM; Jun Jang JIN; Han Sung CHOI; Chang Ju KIM; Il Gyu KO

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Pentoxifylline Alleviates Perinatal Hypoxic-Ischemia-Induced Short-term Memory Impairment by Suppressing Apoptosis in the Hippocampus of Rat Pups.

Author: Je Hoon PARK ¹ ; Sung Eun KIM ; Jun Jang JIN ; Han Sung CHOI ; Chang Ju KIM ; Il Gyu KO
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1. Department of Surgery, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon, Korea.
Publication Type:Original Article
Keywords: Hypoxia-Ischemia; Pentoxifylline; Phosphodiesterase-4 Inhibitors; Memory; Cyclic AMP; Apoptosis
MeSH: Adenosine Monophosphate; Animals; Apoptosis*; Blotting, Western; Brain; Caspase 3; Cell Death; Child; Cyclic AMP; DNA Fragmentation; Hippocampus*; Humans; Immunohistochemistry; Infant; Infant, Newborn; Memory; Memory, Short-Term*; Mortality; Neurons; Pentoxifylline*; Rats*
From:International Neurourology Journal 2016;20(2):107-113
CountryRepublic of Korea
Language:English
Abstract: PURPOSE: 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.