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Key Event Title
Occurrence, Focal Seizure
|Level of Biological Organization|
Key Event Components
|EEG with focal epileptiform discharges||neuron||occurrence|
Key Event Overview
AOPs Including This Key Event
Key Event Description
This key event is characterized as the start of synchronized neural signaling in a specific group of neurons. It is possible that when the ratio between excitatory (glutamatergic) over inhibitory (GABAergic) currents in brain tissue increases past the threshold of the network , seizure starts to occur (Miller, 2015). The initial occurrence of epileptiform activity, in specific regions of the brain, can begin a signaling cascade leading to seizure spread throughout the brain (i.e., secondary generalization leading to status epilepticus) (Kandel et al., 2013).
Acetylcholinesterase inhibition induced seizure
For the signaling cascade caused by acetylcholinesterase inhibition to continue to propagate, some studies suggest that stimulation specifically in the basolateral amygdala plays a key role in the development of seizure activity (McDonough Jr and Shih, 1997). Other studies indicate that the piriform cortex as well as the hippocampus also play a role in seizure development caused by nerve agents (Myhrer, 2007).
How It Is Measured or Detected
- An electrocorticogram record can be used to measure brain activity to monitor seizure development (Braitman and Sparenborg, 1989).
- Brain electroencephalographic (EEG) activity can also record the development of the seizure (Acon-Chen et al., 2016; Kandel et al., 2013).
- Whole cell recordings of spontaneous inhibitory postsynaptic currents and excitatory postsynaptic currents have also been used to study the initial seizures occurring from exposure to organophosphates (Miller, 2015).
Domain of Applicability
Seizures have been observed and studied in many different species including vertebrate and invertebrates. Listed species above are specifically referenced in the cited sources.
There is evidence indicating that in developing rat brains GABAergic activity might be excitatory, not inhibitory (Li and Xu, 2008). Increased sensitivity shown by younger individuals to some substances that induce seizures may possibly be affected by this phenomenon (Miller, 2015).
Both males and females can develop focal seizures, with some possible differences in sensitivity to certain forms of epileptic activity (Belelli et al., 1990). Despite some differences the effect of the key event is conserved for both sexes.
Acon-Chen, C., J. A. Koenig, G. R. Smith, A. R. Truitt, T. P. Thomas and T. M. Shih (2016), "Evaluation of acetylcholine, seizure activity and neuropathology following high-dose nerve agent exposure and delayed neuroprotective treatment drugs in freely moving rats”, Toxicology Mechanisms and Methods 26(5): 378-388. DOI: 10.1080/15376516.2016.1197992.
Belelli, D., N. C. Lan and K. W. Gee (1990), "Anticonvulsant steroids and the GABA/benzodiazepine receptor-chloride ionophore complex”, Neuroscience & Biobehavioral Reviews 14(3): 315-322. DOI: https://doi.org/10.1016/S0149-7634(05)80041-7.
Braitman, D. J. and S. Sparenborg (1989), "MK-801 protects against seizures induced by the cholinesterase inhibitor soman”, Brain Research Bulletin 23(1-2): 145-148. DOI: 10.1016/0361-9230(89)90173-1.
Kandel, E., J. Schwartz, T. Jessell, S. Siegelbaum and A. J. Hudspeth (2013), “Seizures and Epilepsy”, in Principles of Neural Science, Fifth Edition, Blacklick, United States, McGraw-Hill Publishing: 1116-1139.
Li, K. and E. Xu (2008), "The role and the mechanism of gamma-aminobutyric acid during central nervous system development”, Neuroscience bulletin 24(3): 195-200. DOI: 10.1007/s12264-008-0109-3.
McDonough Jr, J. H. and T. M. Shih (1997), "Neuropharmacological mechanisms of nerve agent-induced seizure and neuropathology”, Neuroscience and Biobehavioral Reviews 21(5): 559-579. DOI: 10.1016/S0149-7634(96)00050-4.
Miller, S. L. (2015), The Efficacy of LY293558 in Blocking Seizures and Associated Morphological, and Behavioral Alterations Induced by Soman in Immature Male Rats and the Role of the M1 Muscarinic Acetylcholine Receptor in Organophosphate Induced Seizures. Doctor of philosophy in the neuroscience graduate program Doctoral dissertation, Uniformed Services University.
Myhrer, T. (2007), "Neuronal structures involved in the induction and propagation of seizures caused by nerve agents: Implications for medical treatment”, Toxicology 239(1-2): 1-14. DOI: 10.1016/j.tox.2007.06.099.