Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, et al. A definition and classification of status epilepticus—Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56:1515–23.

Article  PubMed  Google Scholar 

Johnson EL, Kaplan PW. Status epilepticus: definition, classification, pathophysiology, and epidemiology. Semin Neurol. 2020;40:647–51.

Article  PubMed  Google Scholar 

Ascoli M, Ferlazzo E, Gasparini S, Mastroianni G, Citraro R, Roberti R, et al. Epidemiology and outcomes of status epilepticus. Int J Gen Med. 2021;14:2965–73.

Article  PubMed  PubMed Central  Google Scholar 

Zimmern V, Korff C. Status epilepticus in children. J Clin Neurophysiol. 2020;37:429–33.

Article  PubMed  Google Scholar 

Dhaliwal JS, Rosani A, Saadabadi A Diazepam. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023.

Burman RJ, Selfe JS, Lee JH, van den Berg M, Calin A, Codadu NK, et al. Excitatory GABAergic signalling is associated with benzodiazepine resistance in status epilepticus. Brain. 2019;142:3482–501.

Article  PubMed  PubMed Central  Google Scholar 

Brigo F, Del Giovane C, Nardone R, Trinka E, Lattanzi S. Intravenous antiepileptic drugs in adults with benzodiazepine-resistant convulsive status epilepticus: A systematic review and network meta-analysis. Epilepsy Behav. 2019;101:106466.

Article  PubMed  Google Scholar 

Tang Y, Feng B, Wang Y, Sun H, You Y, Yu J, et al. Structure-based discovery of CZL80, a caspase-1 inhibitor with therapeutic potential for febrile seizures and later enhanced epileptogenic susceptibility. Br J Pharmacol. 2020;177:3519–34.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhao J, Zheng Y, Liu K, Chen J, Lai N, Fei F, et al. HMGB1 is a therapeutic target and biomarker in diazepam-refractory status epilepticus with wide time window. Neurotherapeutics. 2020;17:710–21.

Article  CAS  PubMed  Google Scholar 

Ruan Y, Xu C, Lan J, Nao J, Zhang S, Fan F, et al. Low-frequency stimulation at the subiculum is anti-convulsant and anti-drug-resistant in a mouse model of lamotrigine-resistant temporal lobe epilepsy. Neurosci Bull. 2020;36:654–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu C, Zhang S, Gong Y, Nao J, Shen Y, Tan B, et al. Subicular caspase-1 contributes to pharmacoresistance in temporal lobe epilepsy. Ann Neurol. 2021;90:377–90.

Article  CAS  PubMed  Google Scholar 

Tan CC, Zhang JG, Tan MS, Chen H, Meng DW, Jiang T, et al. NLRP1 inflammasome is activated in patients with medial temporal lobe epilepsy and contributes to neuronal pyroptosis in amygdala kindling-induced rat model. J Neuroinflammation. 2015;12:18.

Article  PubMed  PubMed Central  Google Scholar 

Qin Z, Song J, Lin A, Yang W, Zhang W, Zhong F, et al. GPR120 modulates epileptic seizure and neuroinflammation mediated by NLRP3 inflammasome. J Neuroinflammation. 2022;19:121.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mohseni-Moghaddam P, Roghani M, Khaleghzadeh-Ahangar H, Sadr SS, Sala C. A literature overview on epilepsy and inflammasome activation. Brain Res Bull. 2021;172:229–35.

Article  CAS  PubMed  Google Scholar 

Wolf BB, Green DR. Suicidal tendencies: apoptotic cell death by caspase family proteinases. J Biol Chem. 1999;274:20049–52.

Article  CAS  PubMed  Google Scholar 

Yu P, Zhang X, Liu N, Tang L, Peng C, Chen X. Pyroptosis: mechanisms and diseases. Signal Transduct Target Ther. 2021;6:128.

Article  PubMed  PubMed Central  Google Scholar 

Xia S, Yang P, Li F, Yu Q, Kuang W, Zhu Y, et al. Chaihu-Longgu-Muli Decoction exerts an antiepileptic effect in rats by improving pyroptosis in hippocampal neurons. J Ethnopharmacol. 2021;270:113794.

Article  CAS  PubMed  Google Scholar 

Xia L, Liu L, Cai Y, Zhang Y, Tong F, Wang Q, et al. Inhibition of gasdermin D-mediated pyroptosis attenuates the severity of seizures and astroglial damage in kainic acid-induced epileptic mice. Front Pharmacol. 2021;12:751644.

Article  CAS  PubMed  Google Scholar 

Xu ZH, Wang Y, Tao AF, Yu J, Wang XY, Zu YY, et al. Interleukin-1 receptor is a target for adjunctive control of diazepam-refractory status epilepticus in mice. Neuroscience. 2016;328:22–9.

Article  CAS  PubMed  Google Scholar 

Cristina de Brito Toscano E, Leandro Marciano Vieira É, Boni Rocha Dias B, Vidigal Caliari M, Paula Gonçalves A, Varela Giannetti A, et al. NLRP3 and NLRP1 inflammasomes are up-regulated in patients with mesial temporal lobe epilepsy and may contribute to overexpression of caspase-1 and IL-β in sclerotic hippocampi. Brain Res. 2021;1752:147230.

Article  CAS  PubMed  Google Scholar 

Ravizza T, Noé F, Zardoni D, Vaghi V, Sifringer M, Vezzani A. Interleukin Converting Enzyme inhibition impairs kindling epileptogenesis in rats by blocking astrocytic IL-1beta production. Neurobiol Dis. 2008;31:327–33.

Article  CAS  PubMed  Google Scholar 

Maroso M, Balosso S, Ravizza T, Iori V, Wright CI, French J, et al. Interleukin-1β biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice. Neurotherapeutics. 2011;8:304–15.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang B, Zou J, Rensing NR, Yang M, Wong M. Inflammatory mechanisms contribute to the neurological manifestations of tuberous sclerosis complex. Neurobiol Dis. 2015;80:70–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Viviani B, Bartesaghi S, Gardoni F, Vezzani A, Behrens MM, Bartfai T, et al. Interleukin-1beta enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci. 2003;23:8692–700.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Balosso S, Maroso M, Sanchez-Alavez M, Ravizza T, Frasca A, Bartfai T, et al. A novel non-transcriptional pathway mediates the proconvulsive effects of interleukin-1beta. Brain. 2008;131:3256–65.

Article  PubMed  PubMed Central  Google Scholar 

Zipp F, Bittner S, Schafer DP. Cytokines as emerging regulators of central nervous system synapses. Immunity. 2023;56:914–25.

Article  CAS  PubMed  Google Scholar 

Callus BA, Vaux DL. Caspase inhibitors: viral, cellular and chemical. Cell Death Differ. 2007;14:73–8.

Article  CAS  PubMed  Google Scholar 

Vezzani A, Balosso S, Maroso M, Zardoni D, Noé F, Ravizza T. ICE/caspase 1 inhibitors and IL-1beta receptor antagonists as potential therapeutics in epilepsy. Curr Opin Investig Drugs. 2010;11:43–50.

CAS  PubMed  Google Scholar 

Pan L, Tang WD, Wang K, Fang QF, Liu MR, Wu ZX, et al. Novel caspase-1 inhibitor CZL80 improves neurological function in mice after progressive ischemic stroke within a long therapeutic time-window. Acta Pharmacol Sin. 2022;43:2817–27.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu D, Tang Y, Li W, You Y, Shi J, Xu C, et al. Thermo-sensitive micelles extend therapeutic potential for febrile seizures. Signal Transduct Target Ther. 2021;6:296.

Article  PubMed  PubMed Central  Google Scholar 

George Paxinos KBJF. The mouse brain in stereotaxic coordinates. New York: Academic Press; 2007.

Wang Y, Qiu XY, Liu JY, Tan B, Wang F, Sun MJ, et al. (+)-Borneol enantiomer ameliorates epileptic seizure via decreasing the excitability of glutamatergic transmission. Acta Pharmacol Sin. 2023;44:1600–11.

Article  CAS  PubMed  Google Scholar 

Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med. 1998;339:792–8.

Article  CAS  PubMed  Google Scholar 

Treiman DM, Walton NY, Kendrick C. A progressive sequence of electroencephalographic changes during generalized convulsive status epilepticus. Epilepsy Res. 1990;5:49–60.

Article  CAS  PubMed  Google Scholar 

Xu C, Wang S, Wang Y, Lin K, Pan G, Xu Z, et al. A decrease of ripples precedes seizure onset in mesial temporal lobe epilepsy. Exp Neurol. 2016;284:29–37.

Article  PubMed  Google Scholar 

Müller CJ, Gröticke I, Bankstahl M, Löscher W. Behavioral and cognitive alterations, spontaneous seizures, and neuropathology developing after a pilocarpine-induced status epilepticus in C57BL/6 mice. Exp Neurol. 2009;219:284–97.

Article  PubMed  Google Scholar 

Chen JW, Wasterlain CG. Status epilepticus: pathophysiology and management in adults. Lancet Neurol. 2006;5:246–56.

Article  PubMed  Google Scholar 

Bragin A, Azizyan A, Almajano J, Wilson CL, Engel J Jr. Analysis of chronic seizure onsets after intrahippocampal kainic acid injection in freely moving rats. Epilepsia. 2005;46:1592–8.