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An increase in the abundance of individual proinflammatory molecules including interleukin 1 beta has been observed in brain tissue samples of patients with pharmacoresistant temporal lobe epilepsy (TLE) and corresponding animal models. The NLRP3-inflammasome, a cytosolic protein complex, acts as a key regulator in proinflammatory innate immune signalling. Upon activation, it leads to the release of interleukin 1 beta and inflammation-mediated neurodegeneration. Transient brain insults, like status epilepticus (SE), can render hippocampi chronically hyperexcitable and induce segmental neurodegeneration. The underlying mechanisms are referred to as epileptogenesis. Here, we have tested the hypothesis that distinct NLRP3-dependent transcript and protein signalling dynamics are induced by SE and whether they differ between two classical SE models. We further correlated the association of NLRP3-related transcript abundance with convulsive activity in human TLE hippocampi of patients with and without associated neurodegenerative damage.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>Hippocampal mRNA- and protein-expression of NLRP3 and associated signalling molecules were analysed longitudinally in pilocarpine- and kainic acid-induced SE TLE mouse models. Complementarily, we studied NLRP3 inflammasome-associated transcript patterns in epileptogenic hippocampi with different damage patterns of pharmacoresistant TLE patients that had undergone epilepsy surgery for seizure relief.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>Pilocarpine- and kainic acid-induced SE elicit distinct hippocampal<jats:italic>Nlrp3<\/jats:italic>-associated molecular signalling. Transcriptional activation of NLRP3 pathway elements is associated with seizure activity but independent of the particular neuronal damage phenotype in KA-induced and in human TLE hippocampi.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Significance<\/jats:title><jats:p>These data suggest highly dynamic inflammasome signalling in SE-induced TLE and highlight a vicious cycle associated with seizure activity. Our results provide promising perspectives for the inflammasome signalling pathway as a target for anti-epileptogenic and -convulsive therapeutic strategies. The latter may even applicable to a particularly broad spectrum of TLE patients with currently pharmacoresistant disease.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0271995","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T17:28:41Z","timestamp":1660670921000},"page":"e0271995","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":56,"title":["Characterisation of NLRP3 pathway-related neuroinflammation in temporal lobe epilepsy"],"prefix":"10.1371","volume":"17","author":[{"given":"Malin 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Pitk\u00e4nen","year":"2014","journal-title":"Neurotherapeutics"},{"key":"pone.0271995.ref003","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1002\/ana.25205","article-title":"Getting the best outcomes from epilepsy surgery","volume":"83","author":"VN Vakharia","year":"2018","journal-title":"Annals of Neurology"},{"issue":"7","key":"pone.0271995.ref004","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1111\/epi.12220","article-title":"International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: A Task Force report from the ILAE Commission on Diagnostic Methods","volume":"54","author":"I Bl\u00fcmcke","year":"2013","journal-title":"Epilepsia"},{"issue":"8","key":"pone.0271995.ref005","doi-asserted-by":"crossref","first-page":"5446","DOI":"10.1007\/s12035-015-9465-y","article-title":"The Severity of Gliosis in Hippocampal Sclerosis Correlates with Pre-Operative Seizure Burden and Outcome After Temporal 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lobe epilepsy and may contribute to overexpression of caspase-1 and IL-\u03b2 in sclerotic hippocampi","volume":"1752","author":"E Cristina de Brito Toscano","year":"2021","journal-title":"Brain Res"},{"issue":"7","key":"pone.0271995.ref025","first-page":"779","article-title":"NLRP3 inflammasome and endoplasmic reticulum stress in the epileptogenic zone in temporal lobe epilepsy: molecular insights into their interdependence","volume":"46","author":"J Yue","year":"2020","journal-title":"Neuropathol Appl Neurobiol"},{"issue":"7","key":"pone.0271995.ref026","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1080\/01926230701748305","article-title":"Mesial temporal lobe epilepsy: Pathogenesis, induced rodent models and lesions","volume":"35","author":"AK Sharma","year":"2007","journal-title":"Toxicol Pathol"},{"issue":"3","key":"pone.0271995.ref027","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1007\/s12035-018-1181-y","article-title":"Anti-epileptogenic and 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Sofroniew","year":"2014","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"2","key":"pone.0271995.ref040","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1007\/s00429-014-0962-y","article-title":"The subpopulation of microglia expressing functional muscarinic acetylcholine receptors expands in stroke and Alzheimer\u2019s disease","volume":"221","author":"M Pannell","year":"2016","journal-title":"Brain Struct Funct"},{"issue":"3","key":"pone.0271995.ref041","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1159\/000493332","article-title":"Activation of M 3 muscarinic acetylcholine receptors delayed cardiac aging by inhibiting the Caspase-1\/IL-1\u03b2 Signaling Pathway","volume":"49","author":"S Wang","year":"2018","journal-title":"Cell Physiol Biochem"},{"issue":"23","key":"pone.0271995.ref042","doi-asserted-by":"crossref","first-page":"10923","DOI":"10.18632\/aging.102495","article-title":"Kainic acid hyperphosphorylates tau via inflammasome activation 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