Propentofylline protects neurons in culture from death triggered by macrophage or microglial secretory products.
We recently demonstrated that conditioned medium (CM) from peritoneal macrophages or activated microglia triggers a predominantly apoptotic death in hippocampal neurons in culture. We tested the effects of propentofylline (ppf), an agent that is neuroprotective in focal ischemia and is also associated with reduced microglial antigen expression after insult. Ppf had no impact on the secretion of neurotoxin from microglia. However, ppf significantly attenuated the effects of macrophage and microglial conditioned medium on neurons. Ppf did not attenuate neuronal hypoxic injury but did reverse the exaggeration of hypoxic injury exerted by subsequent addition of macrophage CM. A1 and A2 adenosine receptor inhibitors and an inhibitor of adenosine uptake each mimicked the effect of ppf. Neither ATP nor a deaminase inhibitor blocked the effect of microglial CM. These findings may be relevant to the neuroprotective effects of ppf in ischemia and dementia.
Flavin
M P
MP
Department of Pediatrics, Queen's University, Kingston, Ontario, Canada. mf6@post.queensu.ca
Ho
L T
LT
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000502:physiology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005333:Fetus; D006624:Hippocampus / Q000166:cytology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014970:Xanthines / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D018696:Neuroprotective Agents; D014970:Xanthines; C010192:9-(2-hydroxy-3-nonyl)adenine; C032114:propentofylline; D000255:Adenosine Triphosphate; D000225:Adenine; D000241:Adenosine