G Lallement

..In summary, these observations confirm that ketamine, either racemic or S-KET, in association with AS and possibly other drugs, could be highly effective in the delayed treatment of severe soman intoxication...

..Thus, replacing PYR by HUP for a subchronic pre-treatment of primates gives them better tolerance to the epileptic effects of soman...

..Finally, recent data, showing that HUP seems to be devoid of deleterious effects in healthy subjects, are also presented. Globally, this review reinforces the therapeutical value of HUP for the optimal pretreatment of OP poisoning...

..7 micromol diazepam/kg. Reflections on the possible incorporation of avizafone in three-drug emergency treatment are presented...

..However, it should always be kept in mind that, in the case of severe OP-poisoning, medical intervention must be conducted as early as possible...

..Considerations about huperzine or physostigmine + scopolamine as the most appropriate candidate for the pretreatment of OP poisoning are given...

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..Only treatment with tritherapy (atropine + TCP + NBQX) was able to improve the different parameters of spatial learning, despite no effect on the convulsions of the animals...

..So we can hypothesize, that the variation of energy in gamma band after intoxication, which might be related to stress adaptation strategy, may determine whether or not the animal will exhibit an epileptic fit...

..Finally, at the light of its particular inhibitory effects on blood and central cholinesterases, HUP, compared to the other drugs, seems to be the optimal candidate to be used as pretreatment against OP poisoning...

..This dose of HUP reduced AChE inhibition to 54% and increase of ACh level to 230 times baseline value. HUP thus appears as a promising compound to protect subjects against organophosphorus intoxication...

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..However, supplementary pre-medication, in addition to paraldehyde and atropine sulfate, remains necessary to improve the antilethal capacity of the pre-treatment...

..Altogether, PDX-induced uptake impairment may thus be related to the direct action of AA and other PUFAs on the glutamate transporter, as well as through less selective actions...

..Nature of the organ(s) and mechanisms involved in enzyme release will need further investigations as it may represent a mechanism of defence, i.e. VX scavenging, that could advantageously be exploited...

..Further studies are strongly required...

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..Long-term effects of SM burn were also evaluated. The model was then used in the companion paper (Taysse et al.(1))...

..Globally, the current lack of any other NMDA receptor antagonist suitable for human use reinforces the therapeutic value of gacyclidine as a central nervous system protective agent for the treatment of OP poisoning...

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..However, there exists a large amount of data in the model on anaesthesia and different types of shock favouring their use for evaluation of complex situations such as the anaesthesia of OP poisoned patients and combined injuries...

..At the same time, learning skills slightly recovered in the HWL group. Mnemonic cognitive data are discussed in relation to the neuropathology, neurogenesis and sprouting occurring in the hippocampus of soman-intoxicated animals...

..This latter behavioral result is in accordance with the delayed neuronal regeneration patterns described in the companion paper (part 1)...

..In soman poisoning as well as in other cerebral pathologies, premature conclusions on this question can potentially be misleading and might even lead to detrimental therapies...

..e., when KET efficacy is dramatically reduced. All in all, these observations suggest that KET, in association with atropine sulfate and possibly other drugs, may be highly effective in the delayed treatment of severe soman intoxication...

..In conclusion, the present study indicates a quick neuro-inflammatory gene response that does not subside over 7 days suggesting a potential role in the neurological consequences of soman-induced status epilepticus...

..It thus appears that subchronic administration of huperzine A did not induce deleterious effects on spatial memory...

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..In the light of these findings, it seems premature to definitely reject (or recommend) Flu as a possible adjuvant medication against soman poisoning. Further studies are required to determine its real potential interest...

..We observed an increase of energy in the EEG theta band during 3 days after soman injection and an increase of slow wave sleep during the second to the fifth day after soman injection...

..In the companion paper (see part 2), the possible effects of both long-term neuropathology and delayed neuronal regeneration were evaluated on amygdala-driven emotional processes...

..Other approaches would be required to resolve this question...

..Interestingly, the administration of cytokines resulted in the differentiation of BrdU-positive cells into new neurons in the CA1 hippocampal layer, whereas astrocytic differentiation was preferentially observed in the amygdala...

..e. CA1 field and amygdala) evidencing the formation of a glial scar. In this study, we discuss the key role of VEGF in the angiogenic process and in the glial or neuronal response induced by soman poisoning...

..In this study, we discuss the potential use of NeuN immunohistochemistry as a good biomarker to predict delayed neuronal degeneration in the rodent hippocampus after various brain injuries...

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..This increased proliferation rate was detected up to 1 month after poisoning...

..However, this drug also diminished the proliferation of neural precursor cells. The possible neurochemical mechanisms underlying such differences in the efficacy of the two drugs are also reviewed...