Assessment of brain oxygenation imbalance following soman exposure in rats

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

doi:10.1016/j.neuro.2018.01.007

Assessment of brain oxygenation imbalance following soman exposure in rats

Neurotoxicology. 2018 Mar:65:28-37. doi: 10.1016/j.neuro.2018.01.007. Epub 2018 Jan 31.

Authors

Kevin Lee¹, Sara Bohnert², Ying Wu¹, Cory Vair², John Mikler², G Campbell Teskey¹, Jeff F Dunn³

Affiliations

¹ Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
² Defence Research and Development Canada- Suffield Research Centre, Department of National Defence, Suffield, Alberta, Canada.
³ Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address: dunnj@ucalgary.ca.

PMID: 29378300
DOI: 10.1016/j.neuro.2018.01.007

Abstract

Nerve agents (NAs) are potent organophosphorus (OP) compounds with applications in chemical warfare. OP compounds act by inhibiting acetylcholinesterase (AChE). Soman (O-pinacolyl methylphosphonofluoridate) is one of the most potent NAs. It is well known that small doses of NAs can be lethal, and that even non-lethal exposure leads to long-term mental debilitation/neurological damage. However, the neuropathology following exposure to sub-lethal nerve agents is not well understood. In this study, we examined changes in tissue oxygenation (pO₂) in the cortex and hippocampus after a sub-lethal dose of soman [80-90 μg/kg; subcutaneous]. pO₂ changes can provide information regarding oxygen delivery and utilization and may be indicative of a disruption in cerebral blood flow and/or metabolism. Changes in oxygenation were measured with chronically implanted oxygen sensors in awake and freely moving rats. Measurements were taken before, during, and after soman-induced convulsive seizures. Soman exposure resulted in an immediate increase in pO₂ in the cortex, followed by an even greater increase that precedes the onset of soman-induced convulsive seizures. The rise in hippocampus pO₂ was delayed relative to the cortex, although the general pattern of brain oxygenation between these two regions was similar. After convulsive seizures began, pO₂ levels declined but usually remained hyperoxygenated. Following the decline in pO₂, low frequency cycles of large amplitude changes were observed in both the cortex and hippocampus. This pattern is consistent with recurring seizures. Measuring real-time changes in brain pO₂ provides new information on the physiological status of the brain following soman exposure. These results highlight that the measurement of brain oxygenation could provide a sensitive marker of nerve agent exposure and serve as a biomarker for treatment studies.

Keywords: Cerebral blood flow; Nerve agents; Organophosphates; Oxygenation; Seizures; Soman.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cerebral Cortex / metabolism*
Hippocampus / metabolism*
Implants, Experimental
Male
Monitoring, Ambulatory
Oxygen / metabolism*
Rats
Seizures / chemically induced
Seizures / metabolism
Soman / toxicity*
Time Factors

Substances

Soman
Oxygen