API

Event: 1788

Key Event Title

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Status epilepticus

Short name

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Status epilepticus

Biological Context

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Level of Biological Organization
Individual



Key Event Components

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Process Object Action
secondary generalized seizure brain occurrence

Key Event Overview


AOPs Including This Key Event

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AOP Name Role of event in AOP
AChE Inhibition Leading to Neurodegeneration KeyEvent

Stressors

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Taxonomic Applicability

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Term Scientific Term Evidence Link
rat Rattus norvegicus Moderate NCBI
guinea pig Cavia porcellus Moderate NCBI

Life Stages

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Life stage Evidence
Adult Moderate

Sex Applicability

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Term Evidence
Unspecific Moderate

Key Event Description

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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

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See KE Occurrence, Focal Seizure.


Domain of Applicability

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See KE Occurrence, Focal Seizure.


References

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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.