Hyperosmolar treatment of soman-induced brain lesions in mice: evaluation of the effects through diffusion-weighted magnetic resonance imaging and through histology.
OBJECTIVE
A convulsive dose of soman induces seizure-related brain damage (SRBD), including cerebral edema (CE) and neuronal loss. In the present study on soman-intoxicated mice, we applied diffusion-weighted magnetic resonance imaging (DW-MRI) and quantitative histology, and we measured brain water content to investigate the antiedematous and neuroprotective efficacies of two hyperosmolar treatments: mannitol (Mann) and hypertonic saline (HTS).


METHODS
Mice intoxicated with soman (172 microg/kg after a protective pretreatment) were administered 1 min and 5-h post-challenge an i.v. bolus of saline, of Mann or of HTS. 1 day later, mice were examined with DW-MRI and then sacrificed for brain histology. Additional animals were intoxicated and treated similarly for the measurement of the brain water content (dry/wet weight method).


RESULTS
In intoxicated controls, a significant decrease of the apparent diffusion coefficient (ADC), numerous damaged (eosinophilic) cells, high edema scores, and a significant increase in brain water content were detected 24-h post-challenge in sensitive brain structures. These soman-induced changes were not significantly modified by treatment with Mann or HTS.


CONCLUSIONS
Treatment with hyperosmolar solutions did not reduce the effects of soman on ADC, on cell damage and on CE. Therefore, despite similar treatment protocols, the prominent protection by Mann that was previously demonstrated by others in poisoned rats, was not reproduced in our murine model.
Carpentier
Pierre
P
Centre de Recherches du Service Santé des Armées, Département de Toxicologie, 24 Avenue des Maquis du Grésivaudan, BP 87, F-38702 La Tronche cedex, France.
Testylier
Guy
G
Dorandeu
Frédéric
F
Segebarth
Christoph
C
Montigon
Olivier
O
Foquin
Annie
A
Lahrech
Hana
H
D000818:Animals; D001834:Body Water; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001923:Brain Chemistry / Q000187:drug effects; D001927:Brain Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001929:Brain Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003292:Convulsants / Q000008:administration & dosage / Q000506:poisoning; D038524:Diffusion Magnetic Resonance Imaging; D008297:Male; D008353:Mannitol / Q000627:therapeutic use*; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D012999:Soman / Q000506:poisoning*; D018709:Statistics, Nonparametric
D003292:Convulsants; D018696:Neuroprotective Agents; D012462:Saline Solution, Hypertonic; D008353:Mannitol; D012999:Soman