Reactive mononuclear phagocytes release neurotoxins after ischemic and traumatic injury to the central nervous system.
Reactive microglia and invading macrophages, which appear in brain damaged by stroke or trauma, secrete neuron-killing factors. This release of cytotoxic substances is a delayed process and is not detected until inflammatory cells reach a peak of reactivity by the second day after injury. Proximity to the site of injury and density of mononuclear phagocytes determine in part the amount of neurotoxic activity released by injured tissues. Moreover, drugs that suppress the accumulation of reactive microglia and macrophages also reduce tissue production of neuron poisons. Neurotoxins released by brain inflammatory cells or extracted directly from inflamed tissues are heat-stable, protease-resistant molecules < 500 daltons with actions blocked by N-methyl-D-aspartate (NMDA) receptor antagonists. These molecules are distinguished from free radical intermediates, bind to cation exchange resins, lack carboxyl moieties, and are separated from excitatory amino acids including glutamate or aspartate and from the NMDA receptor-mediated toxin quinolinic acid by ion exchange and reverse phase chromatography. Our data suggest that an unrecognized class of neuron-killing molecules produced by inflammatory cells mediate the delayed neuronal loss associated with stroke and trauma.
Giulian
D
D
Department of Neurology, Baylor College of Medicine, Houston, TX 77030.
Corpuz
M
M
Chapman
S
S
Mansouri
M
M
Robertson
C
C
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002642:Chick Embryo; D002852:Chromatography, Ion Exchange; D017077:Culture Media, Conditioned; D005726:Ganglia, Parasympathetic / Q000166:cytology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017628:Microglia / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D009498:Neurotoxins / Q000302:isolation & purification / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D017077:Culture Media, Conditioned; D007166:Immunosuppressive Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate