Evaluating the organophosphate NIMP on a 3D-brain-on-a-chip system
- Georgetown University, Washington, DC (United States); Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
In the early 1940s, organophosphates used in insecticides were discovered to act as chemical nerve agents. The most common nerve agents are: isopropyl methylphosphonofluoridate (sarin), ethyl dimethylphosphoramidocyanidate (tabun), and S-2-diisopropylaminoethyl O-ethyl methylphosphonothioate (VX). These nerve agents are responsible for causing acetylcholinesterase (AChE) inhibition which leads to acetylcholine gathering in the synapses. This accumulation causes hyperactivity in the nervous system which causes seizures, bradycardia, respiratory paralysis, and eventually death. For this study, the effects of a sarin chemical surrogate, 4-nitrophenyl isopropyl methylphosphonate (NIMP), was evaluated along with the pre-treatment, pyridostigmine bromide (PB) on 3D cultures of human neurons placed on the novel multi-electrode array (MEA). Neuronal spiking and bursting activity was monitored throughout the experiment and levels of cytotoxicity were determined using the lactate dehydrogenase (LDH) assay. In addition, in-vivo analysis was performed for comparison.
- Research Organization:
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
- Sponsoring Organization:
- USDOE National Nuclear Security Administration (NNSA)
- DOE Contract Number:
- AC52-07NA27344
- OSTI ID:
- 1557067
- Report Number(s):
- LLNL-TR-785867; 982122
- Country of Publication:
- United States
- Language:
- English
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