Skip to main content
Erschienen in: Metabolic Brain Disease 3/2015

01.06.2015 | Research Article

Postnatal interleukin-1β administration after experimental prolonged febrile seizures enhances epileptogenesis in adulthood

verfasst von: Mitsumasa Fukuda, Masanori Ito, Yoshiaki Yano, Hisaaki Takahashi, Ryota Motoie, Akiko Yano, Yuka Suzuki, Eiichi Ishii

Erschienen in: Metabolic Brain Disease | Ausgabe 3/2015

Einloggen, um Zugang zu erhalten

Abstract

It remains unclear whether prolonged febrile seizures (pFS) in childhood facilitate mesial temporal lobe epilepsy (MTLE) in adulthood. Interleukin (IL)-1β is associated with seizures in children and immature animal models. Here, we use a rat model of pFS to study the effects of IL-1β on adult epileptogenesis, hippocampal damage, and cognition. We produced prolonged hyperthermia-induced seizures on postnatal days (P) 10–11 and administered IL-1β or saline intranasally immediately after the seizures. Motor and cognitive functions were assessed at P85 using rotarod and passive avoidance tests. Electroencephalogram recordings were conducted at P90 and P120. Hippocampal CA1 and CA3 neurons and gliosis were quantified at the end of the experiment. Spontaneous seizure incidence was significantly greater in rats that had received IL-1β than in those that had received saline or those without hyperthermia-induced seizures (p < 0.05). Seizure frequency did not differ significantly between the three groups and no motor deficits were observed. Passive avoidance learning was impaired in rats that received IL-1β compared with controls (p < 0.05), but was not different from that in rats that received saline. Hippocampal cell numbers and gliosis did not differ between the three groups. These results indicate that neuronal loss and gliosis are not prerequisites for the epileptogenic process that follows pFS. Our results suggest that infantile pFS combined with IL-1β overproduction can enhance adulthood epileptogenesis, and might contribute to the development of MTLE.
Literatur
Zurück zum Zitat Arrode-Bruses G, Bruses JL (2012) Maternal immune activation by poly(I:C) induces expression of cytokines IL-1beta and IL-13, chemokine MCP-1 and colony stimulating factor VEGF in fetal mouse brain. J Neuroinflammation 9:83CrossRefPubMed Arrode-Bruses G, Bruses JL (2012) Maternal immune activation by poly(I:C) induces expression of cytokines IL-1beta and IL-13, chemokine MCP-1 and colony stimulating factor VEGF in fetal mouse brain. J Neuroinflammation 9:83CrossRefPubMed
Zurück zum Zitat Auvin S, Shin D, Mazarati A, Sankar R (2010) Inflammation induced by LPS enhances epileptogenesis in immature rat and may be partially reversed by IL1RA. Epilepsia 51(Suppl 3):34–38CrossRefPubMedCentralPubMed Auvin S, Shin D, Mazarati A, Sankar R (2010) Inflammation induced by LPS enhances epileptogenesis in immature rat and may be partially reversed by IL1RA. Epilepsia 51(Suppl 3):34–38CrossRefPubMedCentralPubMed
Zurück zum Zitat Blümcke I, Pauli E, Clusmann H, Schramm J, Becker A, Elger C, Merschhemke M, Meencke HJ, Lehmann T, von Deimling A, Scheiwe C, Zentner J, Volk B, Romstöck J, Stefan H, Hildebrandt M (2007) A new clinico-pathological classification system for mesial temporal sclerosis. Acta Neuropathol 113:235–244CrossRefPubMedCentralPubMed Blümcke I, Pauli E, Clusmann H, Schramm J, Becker A, Elger C, Merschhemke M, Meencke HJ, Lehmann T, von Deimling A, Scheiwe C, Zentner J, Volk B, Romstöck J, Stefan H, Hildebrandt M (2007) A new clinico-pathological classification system for mesial temporal sclerosis. Acta Neuropathol 113:235–244CrossRefPubMedCentralPubMed
Zurück zum Zitat Cendes F, Kahane P, Brodie M, Andermann F (2012) The mesio-temporal lobe epilepsy syndrome. In: Bureau M, Genton P, Dravet C, Delgado-Escueta AV, Tassinari CA, Thomas P, Wolf P (eds) Epileptic syndrome in infancy, childhood, and adolescence, 5th edn. John Libbery Eurotext Ltd, Paris, pp 383–399 Cendes F, Kahane P, Brodie M, Andermann F (2012) The mesio-temporal lobe epilepsy syndrome. In: Bureau M, Genton P, Dravet C, Delgado-Escueta AV, Tassinari CA, Thomas P, Wolf P (eds) Epileptic syndrome in infancy, childhood, and adolescence, 5th edn. John Libbery Eurotext Ltd, Paris, pp 383–399
Zurück zum Zitat Dubé C, Chen K, Eghbal-Ahmadi M, Brunson K, Soltesz I, Baram TZ (2000) Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long term. Ann Neurol 47:336–344CrossRefPubMedCentralPubMed Dubé C, Chen K, Eghbal-Ahmadi M, Brunson K, Soltesz I, Baram TZ (2000) Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long term. Ann Neurol 47:336–344CrossRefPubMedCentralPubMed
Zurück zum Zitat Dubé C, Vezzani A, Behrens M, Bartfai T, Baram TZ (2005) Interleukin-1β contributes to the generation of experimental febrile seizures. Ann Neurol 57:152–155CrossRefPubMedCentralPubMed Dubé C, Vezzani A, Behrens M, Bartfai T, Baram TZ (2005) Interleukin-1β contributes to the generation of experimental febrile seizures. Ann Neurol 57:152–155CrossRefPubMedCentralPubMed
Zurück zum Zitat Dubé C, Richichi C, Bender RA, Chung G, Littt B, Baram TZ (2006) Temporal lobe epilepsy after experimental prolonged febrile seizures: prospective analysis. Brain 129:911–922CrossRefPubMedCentralPubMed Dubé C, Richichi C, Bender RA, Chung G, Littt B, Baram TZ (2006) Temporal lobe epilepsy after experimental prolonged febrile seizures: prospective analysis. Brain 129:911–922CrossRefPubMedCentralPubMed
Zurück zum Zitat Dubé C, Ravizza T, Hamamura M, Zha Q, Keebaugh A, Fok K, Andres AL, Nalcioglu O, Obenaus A, Vezzani A, Baram TZ (2010) Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers. J Neurosci 30:7484–7494CrossRefPubMedCentralPubMed Dubé C, Ravizza T, Hamamura M, Zha Q, Keebaugh A, Fok K, Andres AL, Nalcioglu O, Obenaus A, Vezzani A, Baram TZ (2010) Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers. J Neurosci 30:7484–7494CrossRefPubMedCentralPubMed
Zurück zum Zitat Fukuda M, Suzuki Y, Ishizaki Y, Kira R, Kikuchi C, Watanabe S, Hino H, Morimoto T, Hara T, Ishii E (2009) Interleukin-1β enhances susceptibility to hyperthermia-induced seizures in developing rats. Seizure 18:211–214CrossRefPubMed Fukuda M, Suzuki Y, Ishizaki Y, Kira R, Kikuchi C, Watanabe S, Hino H, Morimoto T, Hara T, Ishii E (2009) Interleukin-1β enhances susceptibility to hyperthermia-induced seizures in developing rats. Seizure 18:211–214CrossRefPubMed
Zurück zum Zitat Fukuda M, Hino H, Suzuki Y, Takahashi H, Morimoto T, Ishii E (2014) Postnatal interleukin-1β enhances adulthood seizure susceptibility and neuronal cell death after prolonged experimental febrile seizures in infantile rats. Acta Neurol Belg 114:179–185CrossRefPubMed Fukuda M, Hino H, Suzuki Y, Takahashi H, Morimoto T, Ishii E (2014) Postnatal interleukin-1β enhances adulthood seizure susceptibility and neuronal cell death after prolonged experimental febrile seizures in infantile rats. Acta Neurol Belg 114:179–185CrossRefPubMed
Zurück zum Zitat Galic MA, Riazi K, Heida JG, Mouihate A, Fournier NM, Spencer SJ, Kalynchuk LE, Teskey GC, Pittman QJ (2008) Postnatal inflammation increases seizure susceptibility in adult rats. J Neurosci 28:6904–6913CrossRefPubMedCentralPubMed Galic MA, Riazi K, Heida JG, Mouihate A, Fournier NM, Spencer SJ, Kalynchuk LE, Teskey GC, Pittman QJ (2008) Postnatal inflammation increases seizure susceptibility in adult rats. J Neurosci 28:6904–6913CrossRefPubMedCentralPubMed
Zurück zum Zitat Galic MA, Riazi K, Henderson AK, Tsutsui S, Pittman QJ (2009) Viral-like brain inflammation during development causes increased seizure susceptibility in adult rats. Neurobiol Dis 36:343–351CrossRefPubMedCentralPubMed Galic MA, Riazi K, Henderson AK, Tsutsui S, Pittman QJ (2009) Viral-like brain inflammation during development causes increased seizure susceptibility in adult rats. Neurobiol Dis 36:343–351CrossRefPubMedCentralPubMed
Zurück zum Zitat Garay PA, Hsiao EY, Patterson PH, McAllister AK (2012) Maternal immune activation causes age- and region-specific changes in brain cytokines in offspring throughout development. Brain Behav Immun 31:54–68CrossRefPubMedCentralPubMed Garay PA, Hsiao EY, Patterson PH, McAllister AK (2012) Maternal immune activation causes age- and region-specific changes in brain cytokines in offspring throughout development. Brain Behav Immun 31:54–68CrossRefPubMedCentralPubMed
Zurück zum Zitat Ichiyama T, Nishikawa M, Yoshitomi T, Hayashi T, Furukawa S (1998) Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in cerebrospinal fluid from children with prolonged febrile seizures: comparison with acute encephalitis/encephalopathy. Neurology 50:407–411CrossRefPubMed Ichiyama T, Nishikawa M, Yoshitomi T, Hayashi T, Furukawa S (1998) Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in cerebrospinal fluid from children with prolonged febrile seizures: comparison with acute encephalitis/encephalopathy. Neurology 50:407–411CrossRefPubMed
Zurück zum Zitat Kanemoto K, Kawasaki J, Yuasa S, Kumaki T, Tomohiro O, Kaji R, Nishimura M (2003) Increased frequency of interleukin-1β-511 T allele in patients with temporal lobe epilepsy, hippocampal sclerosis, and prolonged febrile convulsion. Epilepsia 44:796–799CrossRefPubMed Kanemoto K, Kawasaki J, Yuasa S, Kumaki T, Tomohiro O, Kaji R, Nishimura M (2003) Increased frequency of interleukin-1β-511 T allele in patients with temporal lobe epilepsy, hippocampal sclerosis, and prolonged febrile convulsion. Epilepsia 44:796–799CrossRefPubMed
Zurück zum Zitat Kira K, Torisu H, Takemoto M, Nomura A, Sakai Y, Sanefuji M, Sakamoto K, Matsumoto S, Gondo K, Hara T (2005) Genetic susceptibility to simple febrile seizures: interleukin-1β promoter polymorphisms are associated with sporadic cases. Neurosci Lett 384:239–244CrossRefPubMed Kira K, Torisu H, Takemoto M, Nomura A, Sakai Y, Sanefuji M, Sakamoto K, Matsumoto S, Gondo K, Hara T (2005) Genetic susceptibility to simple febrile seizures: interleukin-1β promoter polymorphisms are associated with sporadic cases. Neurosci Lett 384:239–244CrossRefPubMed
Zurück zum Zitat Lawrence D (2002) Intranasal delivery could be used to administer drugs directly to the brain. Lancet 359:1674CrossRefPubMed Lawrence D (2002) Intranasal delivery could be used to administer drugs directly to the brain. Lancet 359:1674CrossRefPubMed
Zurück zum Zitat Lee SH, Kim BJ, Kim YB, Chung PW, Moon HS, Suh BC, Yoon WT, Jin DK, Park YS, Lee YT, Park KY (2012) IL-1β induction and IL-6 suppression are associated with aggravated neuronal damage in a lipopolysaccharide-pretreated kainic acid-induced rat pup seizure model. Neuroimmunomodulation 19:319–325CrossRefPubMed Lee SH, Kim BJ, Kim YB, Chung PW, Moon HS, Suh BC, Yoon WT, Jin DK, Park YS, Lee YT, Park KY (2012) IL-1β induction and IL-6 suppression are associated with aggravated neuronal damage in a lipopolysaccharide-pretreated kainic acid-induced rat pup seizure model. Neuroimmunomodulation 19:319–325CrossRefPubMed
Zurück zum Zitat Lewis DV, Shinnar S, Hesdorffer DC, Bagiella E, Bello JA, Chan S, Xu Y, MacFall J, Gomes WA, Moshé SL, Mathern GW, Pellock JM, Nordli DR Jr, Frank LM, Provenzale J, Shinnar RC, Epstein LG, Masur D, Litherland C, Sun S, FEBSTAT Study Team (2014) Hippocampal sclerosis after febrile status epilepticus: the FEBSTAT study. Ann Neurol 75:178–185CrossRefPubMedCentralPubMed Lewis DV, Shinnar S, Hesdorffer DC, Bagiella E, Bello JA, Chan S, Xu Y, MacFall J, Gomes WA, Moshé SL, Mathern GW, Pellock JM, Nordli DR Jr, Frank LM, Provenzale J, Shinnar RC, Epstein LG, Masur D, Litherland C, Sun S, FEBSTAT Study Team (2014) Hippocampal sclerosis after febrile status epilepticus: the FEBSTAT study. Ann Neurol 75:178–185CrossRefPubMedCentralPubMed
Zurück zum Zitat Morimoto T, Kida K, Nagao H, Yoshida K, Fukuda M, Takahashi S (1995) The pathogenic role of the NMDA receptor in hyperthermia-induced seizures in developing rats. Dev Brain Res 84:204–207CrossRef Morimoto T, Kida K, Nagao H, Yoshida K, Fukuda M, Takahashi S (1995) The pathogenic role of the NMDA receptor in hyperthermia-induced seizures in developing rats. Dev Brain Res 84:204–207CrossRef
Zurück zum Zitat Omran A, Peng J, Zhang C, Xiang QL, XueJ GN, Kong H, Yin F (2012) Interleukin-1β and microRNA-146a in an immature rat model and children with mesial temporal lobe epilepsy. Epilepsia 53:1215–1224CrossRefPubMed Omran A, Peng J, Zhang C, Xiang QL, XueJ GN, Kong H, Yin F (2012) Interleukin-1β and microRNA-146a in an immature rat model and children with mesial temporal lobe epilepsy. Epilepsia 53:1215–1224CrossRefPubMed
Zurück zum Zitat Pitkanen A, Sutula TP (2002) Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurol 1:173–181CrossRefPubMed Pitkanen A, Sutula TP (2002) Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurol 1:173–181CrossRefPubMed
Zurück zum Zitat Qulu L, Daniels WM, Mabandia MV (2012) Exposure to prenatal stress enhances the development of seizures in young rats. Metab Brain Dis 27:399–404CrossRefPubMed Qulu L, Daniels WM, Mabandia MV (2012) Exposure to prenatal stress enhances the development of seizures in young rats. Metab Brain Dis 27:399–404CrossRefPubMed
Zurück zum Zitat Ravizza T, Noé F, Zardoni D, Vaghi V, Sifringer M, Vezzani A (2008) Interleukin converting enzyme inhibition impairs kindling epileptogenesis in rats by blocking astrocytic IL-1β production. Neurobiol Dis 31:327–333CrossRefPubMed Ravizza T, Noé F, Zardoni D, Vaghi V, Sifringer M, Vezzani A (2008) Interleukin converting enzyme inhibition impairs kindling epileptogenesis in rats by blocking astrocytic IL-1β production. Neurobiol Dis 31:327–333CrossRefPubMed
Zurück zum Zitat Ravizza T, Balosso S, Vezzani A (2011) Inflammation and prevention of epileptogenesis. Neurosci Lett 497:223–230CrossRefPubMed Ravizza T, Balosso S, Vezzani A (2011) Inflammation and prevention of epileptogenesis. Neurosci Lett 497:223–230CrossRefPubMed
Zurück zum Zitat Sharma AK, Reams RY, Jordan WH, Miller MA, Thacker HL, Snyder PW et al (2007) Mesial temporal lobe epilepsy: pathogenesis, induced rodent models and lesions. Toxicol Pathol 35:984–999CrossRefPubMed Sharma AK, Reams RY, Jordan WH, Miller MA, Thacker HL, Snyder PW et al (2007) Mesial temporal lobe epilepsy: pathogenesis, induced rodent models and lesions. Toxicol Pathol 35:984–999CrossRefPubMed
Zurück zum Zitat Shorvon SD, Goodridge DM (2013) Longitudinal cohort studies of the prognosis of epilepsy: contribution of the National General Practice Study of Epilepsy and other studies. Brain 136:3497–3510CrossRefPubMed Shorvon SD, Goodridge DM (2013) Longitudinal cohort studies of the prognosis of epilepsy: contribution of the National General Practice Study of Epilepsy and other studies. Brain 136:3497–3510CrossRefPubMed
Zurück zum Zitat Tanabe T, Hara K, Shimakawa S, Fukui M, Tamai H (2011) Hippocampal damage after prolonged febrile seizure: one case in a consecutive prospective series. Epilepsia 52:837–840CrossRefPubMed Tanabe T, Hara K, Shimakawa S, Fukui M, Tamai H (2011) Hippocampal damage after prolonged febrile seizure: one case in a consecutive prospective series. Epilepsia 52:837–840CrossRefPubMed
Zurück zum Zitat Vezzani A, Granata T (2005) Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 46:1724–1743CrossRefPubMed Vezzani A, Granata T (2005) Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 46:1724–1743CrossRefPubMed
Zurück zum Zitat Vezzani A, Balosso S, Ravizza T (2008) The role of cytokines in the pathophysiology of epilepsy. Brain Behav Immun 22:797–803CrossRefPubMed Vezzani A, Balosso S, Ravizza T (2008) The role of cytokines in the pathophysiology of epilepsy. Brain Behav Immun 22:797–803CrossRefPubMed
Zurück zum Zitat Viviani B, Bartesaghi S, Gardoni F, Vezzani A, Behrens MM, Bartifai T, Binaglia M, Corsini E, Luca MD, Galli CL, Marinovich M (2003) Interleukin-1β enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci 24:8692–8700 Viviani B, Bartesaghi S, Gardoni F, Vezzani A, Behrens MM, Bartifai T, Binaglia M, Corsini E, Luca MD, Galli CL, Marinovich M (2003) Interleukin-1β enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci 24:8692–8700
Metadaten
Titel
Postnatal interleukin-1β administration after experimental prolonged febrile seizures enhances epileptogenesis in adulthood
verfasst von
Mitsumasa Fukuda
Masanori Ito
Yoshiaki Yano
Hisaaki Takahashi
Ryota Motoie
Akiko Yano
Yuka Suzuki
Eiichi Ishii
Publikationsdatum
01.06.2015
Verlag
Springer US
Erschienen in
Metabolic Brain Disease / Ausgabe 3/2015
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-014-9648-7

Weitere Artikel der Ausgabe 3/2015

Metabolic Brain Disease 3/2015 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Demenzkranke durch Antipsychotika vielfach gefährdet

23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.