Abstract
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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aminopyridines / pharmacology*
-
Apoptosis Regulatory Proteins / antagonists & inhibitors*
-
Apoptosis Regulatory Proteins / physiology
-
Cell Count / methods
-
Cell Death / drug effects*
-
Dose-Response Relationship, Drug
-
Drug Interactions
-
Excitatory Amino Acid Agonists / pharmacology
-
Fluorescent Antibody Technique / methods
-
Humans
-
In Vitro Techniques
-
Membrane Glycoproteins / antagonists & inhibitors*
-
Membrane Glycoproteins / physiology
-
N-Methylaspartate / pharmacology
-
Neocortex / cytology*
-
Neocortex / drug effects
-
Neurons / cytology
-
Neurons / drug effects*
-
Neurons / metabolism
-
Neuroprotective Agents / pharmacology*
-
Propidium
-
TNF-Related Apoptosis-Inducing Ligand
-
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
-
Tumor Necrosis Factor-alpha / physiology
Substances
-
Aminopyridines
-
Apoptosis Regulatory Proteins
-
Excitatory Amino Acid Agonists
-
Membrane Glycoproteins
-
Neuroprotective Agents
-
TNF-Related Apoptosis-Inducing Ligand
-
TNFSF10 protein, human
-
Tumor Necrosis Factor-alpha
-
Propidium
-
N-Methylaspartate
-
flupirtine