eprintid: 1534208
rev_number: 39
eprint_status: archive
userid: 608
dir: disk0/01/53/42/08
datestamp: 2016-12-31 20:08:35
lastmod: 2021-09-26 22:56:09
status_changed: 2019-10-07 14:25:29
type: article
metadata_visibility: show
creators_name: Walker, MC
title: Pathophysiology of status epilepticus
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F81
keywords: Drug resistance, Excitotoxicity, Mitochondria, Reactive oxygen species, Status epilepticus
note: Copyright © 2017 Elsevier Ltd.
abstract: Status epilepticus (SE) is the maximal expression of epilepsy with a high morbidity and mortality. It occurs due to the failure of mechanisms that terminate seizures. Both human and animal data indicate that the longer a seizure lasts, the less likely it is to stop. Recent evidence suggests that there is a critical transition from an ictal to a post-ictal state, associated with a transition from a spatio-temporally desynchronized state to a highly synchronized state, respectively. As SE continues, it becomes progressively resistant to drugs, in particular benzodiazepines due partly to NMDA receptor-dependent internalization of GABA(A) receptors. Moreover, excessive calcium entry into neurons through excessive NMDA receptor activation results in activation of nitric oxide synthase, calpains, and NADPH oxidase. The latter enzyme plays a critical part in the generation of seizure-dependent reactive oxygen species. Calcium also accumulates in mitochondria resulting in mitochondrial failure (decreased ATP production), and opening of the mitochondrial permeability transition pore. Together these changes result in status epilepticus-dependent neuronal death via several pathways. Multiple downstream mechanisms including inflammation, break down of the blood-brain barrier, and changes in gene expression can contribute to later pathological processes including chronic epilepsy and cognitive decline.
date: 2018-02-22
date_type: published
official_url: http://doi.org/10.1016/j.neulet.2016.12.044
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1198918
doi: 10.1016/j.neulet.2016.12.044
pii: S0304-3940(16)30993-4
lyricists_name: Walker, Matthew
lyricists_id: MCWAL61
full_text_status: public
publication: Neuroscience Letters
volume: 667
event_location: Ireland
issn: 1872-7972
citation:        Walker, MC;      (2018)    Pathophysiology of status epilepticus.                   Neuroscience Letters , 667       10.1016/j.neulet.2016.12.044 <https://doi.org/10.1016/j.neulet.2016.12.044>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1534208/1/Walker-M_pathophysiology%20of%20status%20epilepticus-2.pdf