Neuroprotective effects of a catalytic antioxidant in a rat nerve agent model

• Main Authors: Li-Ping Liang, Jennifer N. Pearson-Smith, Jie Huang, Brian J. Day, Manisha Patel
• Format: Article
• Language: English
• Published: Elsevier 2019-01-01
• Series: Redox Biology
• Online Access: http://www.sciencedirect.com/science/article/pii/S2213231718308395

Persistent inhibition of acetylcholinesterase resulting from exposure to nerve agents such as soman, is associated with prolonged seizure activity known as status epilepticus (SE). Without medical countermeasures, exposure to soman and resultant SE leads to high morbidity and mortality. Currently available therapeutics are effective in limiting mortality, however effects on morbidity are highly time-dependent and rely on the ability to suppress SE. We have previously demonstrated significant protection from secondary neuronal injury in surrogate nerve agent models by targeting oxidative stress. However, whether oxidative stress represents a relevant therapeutic target in genuine nerve agent toxicity is unknown. Here, we demonstrate that soman exposure results in robust region- and time-dependent oxidative stress. Targeting this oxidative stress in a post-exposure paradigm using a small molecular weight, broad spectrum catalytic antioxidant, was sufficient to attenuate brain and plasma oxidative stress, neuroinflammation and neurodegeneration. Thus, targeting of oxidative stress in a post-exposure paradigm can mitigate secondary neuronal injury following soman exposure. Keywords: Soman, Oxidative stress, Seizures, Neurodegeneration: microglia activation, Cytokines