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KMID : 1240020160200020107
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International Neurourology Journal
2016 Volume.20 No. 2 p.107 ~ p.113
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Pentoxifylline Alleviates Perinatal Hypoxic-Ischemia-Induced Short-term Memory Impairment by Suppressing Apoptosis in the Hippocampus of Rat Pups
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Park Je-Hoon
Kim Sung-Eun
Jin Jun-Jang
Choi Han-Sung
Kim Chang-Ju
Ko Il-Gyu
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Abstract
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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 3?-5?-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.
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KEYWORD
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Hypoxia-Ischemia, Pentoxifylline, Phosphodiesterase-4 Inhibitors, Memory, Cyclic AMP, Apoptosis
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