Int Neurourol J.  2016 Jun;20(2):107-113. 10.5213/inj.1632532.266.

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

• Park JH
• Kim SE
• Jin JJ
• Choi HS
• Kim CJ
• Ko IG

• KMID: 2365741
• DOI: http://doi.org/10.5213/inj.1632532.266

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 3Í´-5Í´-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.

Keyword

Hypoxia-Ischemia; Pentoxifylline; Phosphodiesterase-4 Inhibitors; Memory; Cyclic AMP; Apoptosis

MeSH Terms

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*
Adenosine Monophosphate
Caspase 3
Cyclic AMP
Pentoxifylline