Attenuation of traumatic cell death by an adenosine A1 agonist in rat hippocampal cells.
In a rat hippocampal cell culture, we studied the mechanism of adenosine-mediated neuroprotection in traumatic injury to neurons. When the processes and bodies of cells in culture were mechanically disrupted, neurons that were located at a distance from the damage site died. This secondary neuronal death is at least partially mediated by glutamate, because MK801, a specific N-methyl-D-aspartate glutamate channel blocker, diminished the toxic effect. Furthermore, cyclopentyl adenosine, a specific A1 adenosine receptor agonist that specifically attenuates synaptic release at the excitatory terminal, also blocked this trauma-mediated cell death. The dissemination of neurotoxicity from cell injury implies a release of a toxin by the dying cells. Consistent with this hypothesis, we found that neurotoxicity could be transferred to an uninjured neuronal culture by applying extracellular solution of the damaged culture to the healthy undamaged culture, as long as the fluid was transferred within 5 minutes. However, the glutamate concentrations in this medium were never higher than 20 nmol/L, suggesting that glutamate is not mediating the soluble and transferable toxicity. Consistent with this observation, the transferable neurotoxicity was not blocked by MK801 but was effectively blocked by cyclopentyl adenosine. Our observations suggest that traumatic cell death in culture is mediated by multiple mechanisms, including glutamate excitotoxicity.
Mitchell
H L
HL
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, Missouri, USA.
Frisella
W A
WA
Brooker
R W
RW
Yoon
K W
KW
D000241:Adenosine / Q000819:agonists*; D000818:Animals; D001930:Brain Injuries / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005110:Extracellular Space / Q000502:physiology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D003470:Culture Media; C053907:8-cyclopentyl-1,3-dimethylxanthine; D016291:Dizocilpine Maleate; D013806:Theophylline; D000241:Adenosine