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Event: 1788

Key Event Title

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

Status epilepticus

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
Status epilepticus
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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
Individual

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
secondary generalized seizure brain 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 Karen Watanabe (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

Focal seizures occur when a small group of neurons start synchronized neural signaling (See KE Occurrence, Focal Seizure). Once started, focal seizures can spread to the entire brain through various axonal pathways. GABA-ergic interneurons help inhibit seizure spread from the seizure focus forming an inhibitory region. If the activity in the focus is intense enough that inhibitory region breaks down and the seizure spreads (Kandel et al., 2013). Once the epileptiform activity has expanded to other areas in the brain, i.e., once both hemispheres of the brain are involved for approximately 5 minutes, the focal seizure has been secondarily generalized (status epilepticus) (Lowenstein and Alldredge, 1998).

Acetylcholinesterase inhibition induced seizure

In the case of acetylcholinesterase inhibition, status epilepticus has been seen to be regulated through NMDAR activation and increasing intracellular Ca2+, which is distinct from the initial focal seizure through mAChRs (Acon-Chen et al., 2016).  Anticholinergic drugs (atropine, 2-PAM…) are ineffective if administrated after seizure generalization, whereas NMDAR antagonists (memantine, MK-801…) can still be effective 35 minutes after exposure (Lallement et al., 1999; McDonough and Shih, 1997). 

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

Domain of Applicability

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

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.

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 Publishing1116-1139.

Lallement, G., D. Clarencon, M. Galonnier, D. Baubichon, M. F. Burckhart and M. Peoc'h (1999), "Acute soman poisoning in primates neither pretreated nor receiving immediate therapy: value of gacyclidine (GK-11) in delayed medical support”, Arch Toxicol 73(2): 115-122. DOI: 10.1007/s002040050595.

Lowenstein, D. H. and B. K. Alldredge (1998), "Status Epilepticus”, New England Journal of Medicine 338(14): 970-976. DOI: 10.1056/nejm199804023381407.

McDonough, J. H., Jr. and T. M. Shih (1997), "Neuropharmacological mechanisms of nerve agent-induced seizure and neuropathology”, Neurosci Biobehav Rev 21(5): 559-579.