Characterizing a mouse model for evaluation of countermeasures against hydrogen sulfide-induced neurotoxicity and neurological sequelae.

Autor: Anantharam P; Department of Veterinary Diagnostic and Animal Production Medicine, Iowa State University, Ames, Iowa., Whitley EM; Pathogenesis LLC, Gainesville, Florida., Mahama B; Department of Veterinary Diagnostic and Animal Production Medicine, Iowa State University, Ames, Iowa., Kim DS; Department of Veterinary Diagnostic and Animal Production Medicine, Iowa State University, Ames, Iowa., Imerman PM; Department of Veterinary Diagnostic and Animal Production Medicine, Iowa State University, Ames, Iowa., Shao D; Department of Veterinary Diagnostic and Animal Production Medicine, Iowa State University, Ames, Iowa., Langley MR; Department of Biomedical Sciences, Iowa State University, Ames, Iowa., Kanthasamy A; Department of Biomedical Sciences, Iowa State University, Ames, Iowa., Rumbeiha WK; Department of Veterinary Diagnostic and Animal Production Medicine, Iowa State University, Ames, Iowa.
Jazyk: angličtina
Zdroj: Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 2017 Jul; Vol. 1400 (1), pp. 46-64. Date of Electronic Publication: 2017 Jul 18.
DOI: 10.1111/nyas.13419
Abstrakt: Hydrogen sulfide (H 2 S) is a highly neurotoxic gas. It is the second most common cause of gas-induced deaths. Beyond mortality, surviving victims of acute exposure may suffer long-term neurological sequelae. There is a need to develop countermeasures against H 2 S poisoning. However, no translational animal model of H 2 S-induced neurological sequelae exists. Here, we describe a novel mouse model of H 2 S-induced neurotoxicity for translational research. In paradigm I, C57/BL6 mice were exposed to 765 ppm H 2 S for 40 min on day 1, followed by 15-min daily exposures for periods ranging from 1 to 6 days. In paradigm II, mice were exposed once to 1000 ppm H 2 S for 60 minutes. Mice were assessed for behavioral, neurochemical, biochemical, and histopathological changes. H 2 S intoxication caused seizures, dyspnea, respiratory depression, knockdowns, and death. H 2 S-exposed mice showed significant impairment in locomotor and coordinated motor movement activity compared with controls. Histopathology revealed neurodegenerative lesions in the collicular, thalamic, and cortical brain regions. H 2 S significantly increased dopamine and serotonin concentration in several brain regions and caused time-dependent decreases in GABA and glutamate concentrations. Furthermore, H 2 S significantly suppressed cytochrome c oxidase activity and caused significant loss in body weight. Overall, male mice were more sensitive than females. This novel translational mouse model of H 2 S-induced neurotoxicity is reliable, reproducible, and recapitulates acute H 2 S poisoning in humans.
(© 2017 New York Academy of Sciences.)
Databáze: MEDLINE
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