Assessment of brain oxygenation imbalance following soman exposure in rats

Lee, Kevin; Bohnert, Sara; Wu, Ying; Vair, Cory; Mikler, John; Teskey, G. Campbell; Dunn, Jeff F.

doi:10.1016/j.neuro.2018.01.007

Cited by 15 publications

(19 citation statements)

References 67 publications

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“…Consistent with our previous study 20 , rats (n = 19) exposed to soman developed generalized tonic-clonic seizures within 7-21 min post exposure. These rats continued to exhibit intermittent mild tremors with rhythmic head movement until imaging at 1 h (n = 9) or 18-24 h (n = 10).…”

Section: Resultssupporting

confidence: 90%

“…We have previously found a decrease in cerebral blood flow throughout the brain 1-h after soman exposure 56 . Despite such a decrease in cerebral blood flow either from neurovascular uncoupling 57 or transient vasoconstriction 20,58 , T 2 did not change. The growing evidence of physiological changes at this time point suggests that early changes in T 2 may be difficult to detect.…”

Section: Resultsmentioning

confidence: 86%

“…Previously, we determined that 90 µg/kg (subcutaneous) of soman consistently induced convulsive seizures in a rodent model 20 . HI-6 dimethanesulfonate (HI-6) (125 mg/kg) and atropine methyl nitrate (AMN) (20 mg/kg), were dissolved in saline, and given as pre- and post-treatment (volume of 1 ml/kg; intraperitoneal) to reduce peripheral soman-related symptoms thereby increasing animal throughput.…”

Section: Methodsmentioning

confidence: 99%

“…The injection site was immediately decontaminated with Reactive Skin Decontamination Lotion and the rat was placed in an observation cage. Rats were observed for the development of soman-related symptoms based on the Suffield rating scale 20 and behavioral seizures using the Racine scale 23 . An additional three doses of the post-treatment regimen were administered at 20-min intervals (intraperitoneal).…”

Section: Methodsmentioning

confidence: 99%

“…The Suffield Rating Scale was used to evaluate soman-related symptoms 20 while the Racine scale was used to measure behavioral seizures 23 . Rats treated with soman were monitored and rated every 10 min for up to 2 h. If the rats were rated 4 or higher on the Suffield Rating Scale, additional observations were required until an improvement was observed for at least two consecutive observation periods.…”

Section: Methodsmentioning

confidence: 99%

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Quantitative T2 MRI is predictive of neurodegeneration following organophosphate exposure in a rat model

Lee

Bohnert

Bouchard

et al. 2020

Sci Rep

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Organophosphorus compounds, such as chemical warfare nerve agents and pesticides, are known to cause neurological damage. This study measured nerve agent-related neuropathology and determined whether quantitative t 2 MRI could be used as a biomarker of neurodegeneration. Quantitative T 2 MRi was performed using a 9.4 T MRI on rats prior to and following soman exposure. T 2 images were taken at least 24 h prior, 1 h and 18-24 h after soman exposure. Rats were pre-and post-treated with HI-6 dimethanesulfonate and atropine methyl nitrate. A multicomponent T 2 acquisition and analysis was performed. Brains were stained with Fluoro-Jade C to assess neurodegeneration. Rats exposed to soman developed behavioral expression of electrographic seizures. At 18-24 h after soman exposure, significant increases in T 2 , a possible marker of edema, were found in multiple regions. The largest changes were in the piriform cortex (before: 47.7 ± 1.4 ms; 18-24 h: 82.3 ± 13.4 ms). Fluoro-Jade C staining showed significant neurodegeneration 18-24 h post exposure. The piriform cortex had the strongest correlation between the change in relaxation rate and percent neurodegeneration (r = 0.96, p < 0.001). These findings indicate there is regionally specific neurodegeneration 24 h after exposure to soman. The high correlation between T 2 relaxivity and histopathology supports the use of T 2 as a marker of injury. Globally, there are up to two million cases of acute pesticide poisoning annually 1. Organophosphorus (OPs) compounds are one of the most widely used pesticides and account for 33% of the pesticides used within the United States in 2012 2. Although new regulations have led to a decrease in OP usage in the United States from 2000 2 , pesticide self-poisoning remains a global health problem in low to middle income countries 1. The ingestion of OPs may account for over 100,000 deaths per year 1. More potent forms of OPs include nerve agents that have been developed as chemical warfare agents. Confirmed usage of nerve agents in Syria, in 2013 and 2017, accounted for the death of hundreds of civilians whilst injuring thousands 3. Nerve agents including tabun, sarin, soman, and VX continue to pose a threat to both civilians and military personnel. Exposure can lead to lacrimation, miosis, tremor, paralysis, convulsive seizures, and respiratory failure, often leading to death if untreated 4. A key problem is that following nerve agent exposure, assessing the extent of brain injury is difficult. A noninvasive method that is sensitive to nerve agent related pathology would allow for the monitoring of patients and determining the efficacy of nerve agent treatment protocols. Current treatment protocols are effective in protecting against lethality; however, they may not prevent nerve agent-related neuropathology and associated long-term sequelae. MRI has been used to assess brain pathology post OP exposure 5-12 but few studies have directly correlated the MR changes to histopathology 7,8,10. Diffusion MRI provides contrast that relates to ce...

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Section: Resultssupporting

confidence: 90%