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Event: 1623

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Occurrence, Focal Seizure

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Occurrence, Focal Seizure
Explore in a Third Party Tool

Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Tissue

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Organ term
brain

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
EEG with focal epileptiform discharges neuron occurrence

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
AChE Inhibition Leading to Neurodegeneration KeyEvent Allie Always (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
rat Rattus norvegicus Moderate NCBI
guinea pig Cavia porcellus Moderate NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Adult Moderate

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific Moderate

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

           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

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help
  • 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

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Taxa

           Seizures have been observed and studied in many different species including vertebrate and invertebrates. Listed species above are specifically referenced in the cited sources.

Age

           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).

Sex

           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.

References

List of the literature that was cited for this KE description. More help

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.