Tumor-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-mediated death of neurons in living human brain tissue is inhibited by flupirtine-maleate.
Neuronal damage mediated by the TRAIL-system might be involved in the pathogenesis of neuroinflammatory diseases of the central nervous system. Here we used an investigator-independent approach to quantify TRAIL-mediated death of total CNS cells and neurons in a living human brain slice culture system, a model which is much closer to the in vivo situation than dissociated cell culture. We observed dose-dependent TRAIL-mediated death of both total human CNS cells and neurons, which was prevented by flupirtine-maleate, a centrally acting analgesic drug with proposed neuroprotective properties. Our data suggest flupirtine-maleate as an orally available neuroprotective approach in the course of neuroinflammation.
Dörr
Jan
J
Institute of Neuroimmunology, Neuroscience Research Center, Charité, University-Medicine, NWFZ 2680, Charité, 10098 Berlin, Germany.
Roth
Karl
K
Zurbuchen
Urte
U
Deisz
Rudolf
R
Bechmann
Ingo
I
Lehmann
Thomas-Nicolas
TN
Meier
Susanne
S
Nitsch
Robert
R
Zipp
Frauke
F
D000631:Aminopyridines / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D019579:Neocortex / Q000166:cytology* / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011419:Propidium; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology
D000631:Aminopyridines; D051017:Apoptosis Regulatory Proteins; D018690:Excitatory Amino Acid Agonists; D008562:Membrane Glycoproteins; D018696:Neuroprotective Agents; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D011419:Propidium; D016202:N-Methylaspartate; C034161:flupirtine