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Key Event Title
|Level of Biological Organization|
Key Event Components
|secondary generalized seizure||brain||occurrence|
Key Event Overview
AOPs Including This Key Event
Key Event Description
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
Domain of Applicability
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 Publishing: 1116-1139.
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.