Status epilepticus leads to Increased, glutamate

Sustained seizure activity that lasts longer than 5 minutes, or repetitive seizures without regaining consciousness constitute status epilepticus (Lowenstein and Alldredge, 1998). Release of glutamate through this sustained seizure activity follows that of KER 1890: Occurrence, Focal Seizure leading to Increased, glutamate.

For AChE inhibition-induced status epilepticus, there are in total three points that differentiate the key events of focal seizure onset (KE 1623) and status epilepticus in the AChE inhibition-induced model of seizure activity: (i) Focal seizures are localized seizures that have not spread/undergone secondary generalization (Kandel et al., 2013). (ii) Status epilepticus has specifically defined requirements that must be met for a subject to be considered to be in status epilepticus, those being that the seizure(s) must have lasted for at least 5 minutes or there are repetitive seizures occurring without the subject regaining function and consciousness (Lowenstein and Alldredge, 1998). The transition between focal seizure activity and generalized status epilepticus occurs somewhere between 5 and 40 minutes after seizure onset (McDonough and Shih, 1997) (iii) The treatment options available for attenuating seizure activity induced by AChE inhibition are best when the seizures initially begin as a focal seizure and reduced when the subject has been in the state of status epilepticus for a prolonged period of time. Specifically, in the early phases of the pathology after exposure to the AChE inhibitor, a cholinergic phase is present, and effective treatment options include both regular anti-seizure treatment and anticholinergic therapy to prevent the seizures from continuing, whereas in the later phase of the pathology, where the seizure activity is now glutamatergically driven, anticholinergic therapy is no longer effective, and the seizure activity can only be effectively treated with the usual therapies (McDonough and Shih, 1997).

Evidence was collected in multiple ways: literature searches of external databases, review of related KEs and KERS in the AOPWiki, and consultation with experts.   Extensive literature searches were conducted in Scopus, Pubmed, and Google Scholar using keywords applicable to each KE, with an initial focus on zebrafish data to then focusing on rat data. Related KEs and KERs in the AOPWiki were also reviewed for relevant evidence and their sources.  The “snowball method” was used to find additional articles, i.e., relevant citations within an article were obtained if they provided additional evidence. EndNote reference managing software was used to store results from the literature searches and when possible, a pdf of the manuscript was attached to each record. Papers were reviewed and categorized by whether they contained data to support one or more parts of the AOP. An Excel spreadsheet was used to record reviewed papers and any information worth noting.

Increases in glutamate release have been shown to occur after the onset of seizure activity (Lallement et al., 1992). See Table 1 in KER 1890: Occurrence, Focal Seizure leading to Increased, glutamate for experiments that measure both seizure activity via electroencephalogram (EEG), and extracellular glutamate during seizure activity.

The papers in Table 1 from the Quantitative Understanding section of KER 1890, Occurrence, Focal Seizure leading to Increased, glutamate  present electroencephalogram (EEG) data from timepoint 0 and onward after local injection of seizure-inducing compounds. The full spectrum of the EEG is not published, and one would need to contact the author as needed.  No additional data found specific to status epilepticus and the release of glutamate.

See KER 1890: Occurrence, Focal Seizure leading to Increased, glutamate.

Kandel, E., Schwartz, J., Jessell, T., Siegelbaum, S. & Hudspeth, A. J. 2013. Seizures and Epilepsy. Principles of Neural Science, Fifth Edition. Blacklick, United States: McGraw-Hill Publishing.

Lallement, G., Denoyer, M., Collet, A., Pernot-Marino, I., Baubichon, D., Monmaur, P. & Blanchet, G. 1992. Changes in hippocampal acetylcholine and glutamate extracellular levels during soman-induced seizures: Influence of septal cholinoceptive cells. Neuroscience Letters, 139, 104-107. DOI: 10.1016/0304-3940(92)90868-8.

Lowenstein, D. H. & Alldredge, B. K. 1998. Status Epilepticus. New England Journal of Medicine, 338, 970-976. DOI: 10.1056/nejm199804023381407.

McDonough, J. H., Jr. & Shih, T. M. 1997. Neuropharmacological mechanisms of nerve agent-induced seizure and neuropathology. Neurosci Biobehav Rev, 21, 559-79. DOI: 10.1016/s0149-7634(96)00050-4.