Sulfur mustard cutaneous injury characterization based on SKH-1 mouse model: relevance of non-invasive methods in terms of wound healing process analyses.

Background: To date, sulphur mustard (SM) cutaneous toxicity has been commonly assessed on account of several animal models such as pigs and weanling pigs. Few experiments however, have been carried out on mice so far. In this study, we aimed at quantifying spontaneous wound healing processes after SM exposure on a SKH-1 mouse model through non-invasive methods over an extended period of time.

Eukaryotic DING proteins are endogenous: an immunohistological study in mouse tissues.

Background: DING proteins encompass an intriguing protein family first characterized by their conserved N-terminal sequences. Some of these proteins seem to have key roles in various human diseases, e.g.

Effects of soman poisoning on mitochondrial respiratory enzyme activity in the mouse hippocampus and cerebral cortex.

Mitochondrial dysfunctions have been highlighted as a contributing factor in epileptic seizures and subsequent neuronal cell death. Soman is an irreversible inhibitor of cholinesterase, triggering epileptic seizures leading to massive neuronal cell death in brain areas, such as the hippocampus and cerebral cortex. Mitochondrial respiratory chain enzymatic assays were performed in hippocampus and cerebral cortex homogenates from mouse brains collected 3 hours, 24 hours, 3 days, and 7 days after soman poisoning.

Long-term consequences of soman poisoning in mice Part 1. Neuropathology and neuronal regeneration in the amygdala.

To date, studies on soman-induced neuropathology mainly focused on the hippocampus, since this brain region is a well-delimited area with easily detectable pyramidal neurons. Moreover, the hippocampus is severely damaged after soman exposure leading to a substantial alteration of behavioral mnemonic processes. The neuropathology described in the hippocampus, however, and its behavioral consequences cannot be extrapolated to all other limbic damaged brain areas such as the amygdala.

Long-term behavioral consequences of soman poisoning in mice.

We investigated the long-term (up to 90 days) consequences of soman intoxication in mice on weight, motor performances (grip strength, rotarod) and mnemonic cognitive processes (T-maze, Morris water maze test). First, a relative weight loss of 20%, measured 3 days after intoxication, was evidenced as a threshold beyond which neuropathological damage was observed in the hippocampus. Animals were then distributed into either low weight loss (LWL) or high weight loss (HWL) groups according to the relative 20% weight loss threshold.

Soman poisoning induces delayed astrogliotic scar and angiogenesis in damaged mouse brain areas.

Gliotic scar formation and angiogenesis are two biological events involved in the tissue reparative process generally occurring in the brain after mechanically induced injury, ischemia or cerebral tumor development. For the first time, in this study, neo-vascularization and glial scar formation were investigated in the brain of soman-poisoned mice over a 3-month period after nerve agent exposure (1.2 LD50 of soman).

Effects of aspirin and mefenamic acid on soman poisoning-induced neuropathology in mice.

The efficacy of aspirin and mefenamic acid to counteract soman-induced brain damage was investigated in mice. Neuronal damage was evaluated in the hippocampus and amygdala by performing omega3 receptor density measurements and hemalun-phloxin staining. The effect of both drugs on the proliferation of neural progenitors after soman exposure was also assessed.

Early reduction of NeuN antigenicity induced by soman poisoning in mice can be used to predict delayed neuronal degeneration in the hippocampus.

The neuronal nuclei (NeuN) antigen is increasingly being used as a specific marker to identify neuronal cell loss under various pathological conditions. However, recent studies pointed out that a decrease in NeuN labeling could also be due to the reduction of protein expression level or loss of antigenicity and this was not necessarily related to neuronal cell disappearance. We also investigated the presence of damaged neurons, the loss of NeuN immunoreactivity and the level of NeuN protein in the brain hippocampus of mice subjected to soman poisoning (1.

Neuronal regeneration partially compensates the delayed neuronal cell death observed in the hippocampal CA1 field of soman-poisoned mice.

Soman poisoning induces long-term neuropathology characterized by the presence of damaged neurons up to 2 months after exposure in various central brain areas, especially the hippocampal CA1 layer. Rapid depletion of this layer could therefore be expected. Surprisingly, the CA1 layer remained consistently visible, suggesting delayed death of these damaged neurons, potentially accompanied by neuronal regeneration.

Soman-induced convulsions: the neuropathology revisited.

The organophosphorus compound soman, an irreversible inhibitor of cholinesterases, produces seizure activity and related brain damage. Studies using various biochemical markers of programmed cell death (PCD) suggested that soman-induced cell damage in the brain was apoptotic rather than necrotic. However, it has recently become clear that not all PCD is apoptotic, and the unequivocal demonstration of apoptosis requires ultrastructural examination.

Efficacy of the ketamine-atropine combination in the delayed treatment of soman-induced status epilepticus.

Nerve agent poisoning is known to induce full-blown seizures, seizure-related brain damage (SRBD), and lethality. Effective and quick management of these seizures is critical. In conditions of delayed treatment, presently available measures are inadequate calling for optimization of therapeutic approaches.

Effect of cytokine treatment on the neurogenesis process in the brain of soman-poisoned mice.

We previously described that enhanced proliferation of neural progenitors occurred in the subgranular zone (SGZ) of the dentate gyrus and in the subventricular zone (SVZ) of the mouse brain following soman poisoning. Then, a discrete number of these cells seemed to migrate and engraft into the main damaged brain regions (hippocampus; septum and amygdala) and subsequently differentiate into neurons. In the present study, the effect of a cytokine treatment on the neurogenesis process was evaluated.

Soman poisoning increases neural progenitor proliferation and induces long-term glial activation in mouse brain.

To date, only short-term glial reaction has been extensively studied following soman or other warfare neurotoxicant poisoning. In a context of cell therapy by neural progenitor engraftment to repair brain damage, the long-term effect of soman on glial reaction and neural progenitor division was analyzed in the present study. The effect of soman poisoning was estimated in mouse brains at various times ranging from 1 to 90 days post-poisoning.

Effect of soman poisoning on populations of bone marrow and peripheral blood cells in mice.

According to recent reports, brain lesions resulting from ischemia, mechanical injury or neurodegenerative diseases can be partially treated using bone marrow-derived stromal cell (BMSC) engraftment approaches. Nevertheless, for brain lesions resulting from organophosphate poisoning, nerve agents such as soman (pinacolyl methylphosphono-fluoridate) could affect blood and bone marrow (BM) micro-environments, thus preventing efficient BMSC migration and engraftment. It is therefore necessary to verify the hematologic response to soman exposure.

Disruption of mice sleep stages induced by low doses of organophosphorus compound soman.

We have explored during 7 days, EEG spectral response and sleep pattern of mice after a mild intoxication with soman. Using an automatic staging method, we have quantified the sleep stage of the mice to identify disruptions of the sleep pattern. The 50 microg/kg dose of soman produced several effects during several time windows after intoxication.

Review of the value of huperzine as pretreatment of organophosphate poisoning.

Today, organophosphate (OP) nerve agents are still considered as potential threats in both military or terrorism situations. OP agents are potent irreversible inhibitors of central and peripheral acetylcholinesterases. Pretreatment of OP poisoning relies on the subchronic administration of the reversible acetylcholinesterase (AChE) inhibitor pyridostigmine (PYR).

Inhibition of crotoxin phospholipase A(2) activity by manoalide associated with inactivation of crotoxin toxicity and dissociation of the heterodimeric neurotoxic complex.

Crotoxin (CACB complex) is a convulsant heterodimeric neurotoxic phospholipase A(2) (PLA(2)). The role of phospholipid hydrolysis in its epileptogenic properties remains unresolved. We, thus, studied the effect of manoalide (MLD), a PLA(2) inhibitor, on the toxin catalytic activity and its central and peripheral toxicity.