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Organophosphorus compounds (OP) are toxic molecules developed as insecticides and chemical warfare nerve agents (CWNAs). Most OP are neurotoxic and act as nervous system disruptors by blocking cholinergic transmission. They are therefore responsible for many poisonings worldwide. OP toxicity may result either from acute or chronic exposure, and their poisoning effect were evaluated using several animal models. These latter were also used for evaluating the efficacy of antidotes. Strategies based on enzymes that can trap (stoichiometric bioscavengers) or degrade (catalytic bioscavengers) OP, were particularly studied since they allow effective decontamination, without toxicity or environmental impact. This review summarizes the results obtained in vivo with enzymes through three levels: prophylaxis, treatment and external decontamination. The efficiency of enzymatic treatments in different animal models is presented and the relevance of these models is also discussed for a better extrapolation to humans.

Poison gas has been the subject of attention from the French army (Grand Quartier General). The 22sd of April 1915, General Joffre decided that the General Direction for Health Service was in charge of the protection of troops against what he called "this new mode of terror, disease, and death". Actions are been launched to found ways for the protection means and to obtain for the army at least equivalent weapons. Pharmacists will have a leading role thanks to their knowledge in chemistry. Research laboratories were working in two areas: individual protection and production of aggressive agents. Paul Lebeau, Gabriel Bertrand, Alexandre Degrez, Charles Moureu were among many others very committed to fight and remains at the top and to react quickly to ennemy's attacks. At the end of the war, Paul Lebeau received the Legion d'Honneur medal for his contribution to war. The school of pharmacy was recognized as faculty of pharmacy, by a decree of May 14th, 1920. The knowledge that were obtained during this period will be used for the second World War, but the chemical weapon was not much used, as opposed to more recent usage in Vietnam, Irak and Syria.

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Chemical weapons represent an ever-growing threat, not only for military forces but also for civilian populations. Nerve agents such as those used in terrorist attacks by the Aum sect in Tokyo are among the deadliest of those non conventional weapons. The French military health service has developed a new auto-injector presenting as a self-usable dual-chamber syringe and successfully obtained a new drug approval to provide this new emergency treatment for the military and civilians. After a short review of the pathophysiology and clinical presentation of acute nerve agent, the authors report the development and the process of new drug application. They finally suggest a clinical guideline for practical use in case of terrorist attack.

Nerve agents could be potentially used as during a conflict or a terrorist attack. If an emergency treatment is not provided after poisoning, irreversible brain damages and behavioural sequels are expected to appear. In vivo cell therapy seems to be a promising approach for delayed treatment to contribute to brain repair. A mobilization of endogenous neural progenitors would be the basis of such an approach. After migrating, these progenitors would engraft in damaged brain regions and subsequently differentiate into functional neurons. In this review, after a few reminders regarding nerve agent poisoning and the emergency treatment of such an intoxication, progresses in terms of cell therapy and its potential application to nerve agent-induced brain lesions are summarized.

Amongst organophosphate compounds, both pesticides and warfare neurotoxics are probably the most representative. These compounds are irreversible acetylcholinesterase inhibitors. Usual clinical signs observed after acute poisoning are mainly respiratory distress, convulsions and seizures. Following acute poisoning, an emergency treatment must be provided as soon as possible (maximum delay of 1 hour post-poisoning), to prevent irreversible brain damage and patient death. At the present time, there is no efficient delayed treatment which could be provided if this 1 hour latency is overpassed. However, neurogenesis by stem cell engraftment, eventually complemented by gene therapy strategy, could be a potential therapeutic approach to repair organophosphate-induced brain damage. Main stem cell engraftement strategies successfully used for brain damage of various origins are reviewed in this Article.

A variety of chemical components can be used as warfare threats directly targeting humans. They can be classified according to their main biological effects as nerve agents, vesicants, lung damaging agents, cyanogen agents and incapacitants. Other chemical agents are water and food contaminants. Still other less aggressive compounds are mainly used to control riots. Smokes, flame materials and herbicides belong to other classes of chemical agents of the warlike armamentum exhibiting a direct effect on man.