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ToxSci Advance Access originally published online on June 23, 2005
Toxicological Sciences 2005 87(1):163-168; doi:10.1093/toxsci/kfi237
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Post-Intoxication Vaccination for Protection of Neurons against the Toxicity of Nerve Agents

Hadas Schori*, Eyal Robenshtok{dagger}, Michal Schwartz*,1 and Ariel Hourvitz{ddagger}

* Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel; {dagger} Department of Internal Medicine E, Rabin Medical Center, Beilinson Campus, Petah-Tikva 49100, Israel; and {ddagger} Israel Defense Force, Medical Corps, Chaim Sheba Medical Center, Tel Hashomer 52621 Israel

Received March 24, 2005; accepted June 7, 2005

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.

Key Words: organophosphate; neuroprotection; neurodegeneration; protective autoimmunity.


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