Post-intoxication vaccination for protection of neurons against the toxicity of nerve agents.
Nerve agents are highly toxic organophosphates (OPs) that can cause severe damage to the central and peripheral nervous systems. The central nervous system insult results in seizures and neuronal death. The glutamatergic system apparently contributes to the neuropathology. Using a model of OP intoxication causing death of retinal ganglion cells in the mouse eye, we show here that intoxication is exacerbated if the mice are devoid of mature T cells. The retinal neurons could be protected from these effects by vaccination, 7 days before or immediately after intoxication, with the copolymer glatiramer acetate (Cop-1), recently found to limit the usual consequences of an acute glutamate insult to the eye. These findings underlie a new therapeutic approach to protection against OP intoxication, based on the rationale that boosting of the adaptive immunity recruited at the site of intoxication helps the local cellular machinery such as resident microglia to withstand the neurotoxic effects.
Schori
Hadas
H
Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel.
Robenshtok
Eyal
E
Schwartz
Michal
M
Hourvitz
Ariel
A
D000818:Animals; D002619:Chemical Warfare Agents / Q000506:poisoning*; D007531:Isoflurophate / Q000506:poisoning*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D010455:Peptides / Q000276:immunology*; D014611:Vaccination
D002619:Chemical Warfare Agents; D010455:Peptides; D007531:Isoflurophate; C021759:(T,G)-A-L