Post-intoxication vaccination for protection of neurons against the toxicity of nerve agents

Hadas Schori, Eyal Robenshtok, Michal Schwartz*, Ariel Hourvitz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)163-168
Number of pages6
JournalToxicological Sciences
Volume87
Issue number1
DOIs
StatePublished - Sep 2005
Externally publishedYes

Keywords

  • Neurodegeneration
  • Neuroprotection
  • Organophosphate
  • Protective autoimmunity

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