Skip to main content
PMC home page
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2012 Jul 11;28(3):301–308. doi: 10.1007/s12264-012-1240-8

IL-1β: an important cytokine associated with febrile seizures?

Hong-Mei Yu 1, Wan-Hong Liu 1, Xiao-Hua He 1, Bi-Wen Peng 1,✉
PMCID: PMC5560328  PMID: 22622830

Abstract

Febrile seizures (FSs) are the most common convulsions in childhood. Studies have demonstrated a significant relationship between a history of prolonged FSs during early childhood and temporal sclerosis, which is responsible for intractable mesial temporal lobe epilepsy. It has been shown that interleukin-1β (IL-1β) is intrinsically involved in the febrile response in children and in the generation of FSs. We summarize the gene polymorphisms, changes of IL-1β levels and the putative role of IL-1β in the generation of FSs. IL-1β could play a role either in enhancing or in reducing neural excitability. If the enhancing and reducing effects are balanced, an FS does not occur. When the enhancing effect plays the leading role, an FS is generated. A mild imbalance can cause simple FSs while a severe imbalance can cause complex FSs and febrile status epilepticus. Therefore, anti-IL-1β therapy may help to treat FSs.

Keywords: febrile seizures, IL-1β, cytokines, gene polymorphism

References

  • [1].Stafstrom C.E. The incidence and prevalence of febrile seizures. In: Baram T.Z., Shinnar S., editors. Febrile Seizures. San Diego, CA: Academic Press; 2002. pp. 325–328. [Google Scholar]
  • [2].Shinnar S. Febrile seizures and mesial temporal sclerosis. Epilepsy Curr. 2003;3:115–118. doi: 10.1046/j.1535-7597.2003.03401.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [3].Addy D.P. Nosology of febrile convulsions. Arch Dis Child. 1986;61:318–320. doi: 10.1136/adc.61.4.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [4].Rossi V., Breviario F., Ghezzi P., Dejana E., Mantovani A. Prostacyclin synthesis induced in vascular cells by interleukin-1. Science. 1985;229:174–176. doi: 10.1126/science.2409598. [DOI] [PubMed] [Google Scholar]
  • [5].Rothwell N.J., Luheshi G.N. Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci. 2000;23:618–625. doi: 10.1016/S0166-2236(00)01661-1. [DOI] [PubMed] [Google Scholar]
  • [6].Corey L.A., Berg K., Pellock J.M., Solaas M.H., Nance W.E., DeLorenzo R.J. The occurrence of epilepsy and febrile seizures in Virginian and Norwegian twins. Neurology. 1991;41:1433–1436. doi: 10.1212/WNL.41.9.1433. [DOI] [PubMed] [Google Scholar]
  • [7].Moos V., Rudwaleit M., Herzog V., Hohlig K., Sieper J., Muller B. Association of genotypes affecting the expression of interleukin-1beta or interleukin-1 receptor antagonist with osteoarthritis. Arthritis Rheum. 2000;43:2417–2422. doi: 10.1002/1529-0131(200011)43:11<2417::AID-ANR7>3.0.CO;2-R. [DOI] [PubMed] [Google Scholar]
  • [8].Pociot F., Molvig J., Wogensen L., Worsaae H., Nerup J. A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur J Clin Invest. 1992;22:396–402. doi: 10.1111/j.1365-2362.1992.tb01480.x. [DOI] [PubMed] [Google Scholar]
  • [9].Kanemoto K., Kawasaki J., Yuasa S., Kumaki T., Tomohiro O., Kaji R., et al. Increased frequency of interleukin-1beta-511T allele in patients with temporal lobe epilepsy, hippocampal sclerosis, and prolonged febrile convulsion. Epilepsia. 2003;44:796–799. doi: 10.1046/j.1528-1157.2003.43302.x. [DOI] [PubMed] [Google Scholar]
  • [10].Kauffman M.A., Moron D.G., Consalvo D., Bello R., Kochen S. Association study between interleukin 1 beta gene and epileptic disorders: a HuGe review and meta-analysis. Genet Med. 2008;10:83–88. doi: 10.1097/GIM.0b013e318161317c. [DOI] [PubMed] [Google Scholar]
  • [11].Virta M., Hurme M., Helminen M. Increased frequency of interleukin-1beta (-511) allele 2 in febrile seizures. Pediatr Neurol. 2002;26:192–195. doi: 10.1016/S0887-8994(01)00380-0. [DOI] [PubMed] [Google Scholar]
  • [12].Kira R., Ishizaki Y., Torisu H., Sanefuji M., Takemoto M., Sakamoto K., et al. Genetic susceptibility to febrile seizures: case-control association studies. Brain Dev. 2010;32:57–63. doi: 10.1016/j.braindev.2009.09.018. [DOI] [PubMed] [Google Scholar]
  • [13].Peltola J., Keranen T., Rainesalo S., Hurme M. Polymorphism of the interleukin-1 gene complex in localization-related epilepsy. Ann Neurol. 2001;50:275–276. doi: 10.1002/ana.1108. [DOI] [PubMed] [Google Scholar]
  • [14].Kira R., Torisu H., Takemoto M., Nomura A., Sakai Y., Sanefuji M., et al. Genetic susceptibility to simple febrile seizures: interleukin-1beta promoter polymorphisms are associated with sporadic cases. Neurosci Lett. 2005;384:239–244. doi: 10.1016/j.neulet.2005.04.097. [DOI] [PubMed] [Google Scholar]
  • [15].Buono R.J., Ferraro T.N., O’Connor M.J., Sperling M.R., Ryan S.G., Scattergood T., et al. Lack of association between an interleukin 1 beta (IL-1beta) gene variation and refractory temporal lobe epilepsy. Epilepsia. 2001;42:782–784. doi: 10.1046/j.1528-1157.2001.42900.x. [DOI] [PubMed] [Google Scholar]
  • [16].Chou I.C., Tsai C.H., Hsieh Y.Y., Peng C.T., Tsai F.J. Association between polymorphism of interleukin-1beta-511 promoter and susceptibility to febrile convulsions in Taiwanese children. Acta Paediatr. 2003;92:1356. doi: 10.1111/j.1651-2227.2003.tb00513.x. [DOI] [PubMed] [Google Scholar]
  • [17].Ozkara C., Uzan M., Tanriverdi T., Baykara O., Ekinci B., Yeni N., et al. Lack of association between IL-1beta/alpha gene polymorphisms and temporal lobe epilepsy with hippocampal sclerosis. Seizure. 2006;15:288–291. doi: 10.1016/j.seizure.2006.02.016. [DOI] [PubMed] [Google Scholar]
  • [18].Tilgen N., Pfeiffer H., Cobilanschi J., Rau B., Horvath S., Elger C.E., et al. Association analysis between the human interleukin 1beta (-511) gene polymorphism and susceptibility to febrile convulsions. Neurosci Lett. 2002;334:68–70. doi: 10.1016/S0304-3940(02)01069-8. [DOI] [PubMed] [Google Scholar]
  • [19].Matsuo M., Sasaki K., Ichimaru T., Nakazato S., Hamasaki Y. Increased IL-1beta production from dsRNA-stimulated leukocytes in febrile seizures. Pediatr Neurol. 2006;35:102–106. doi: 10.1016/j.pediatrneurol.2005.12.005. [DOI] [PubMed] [Google Scholar]
  • [20].Tsai F.J., Hsieh Y.Y., Chang C.C., Lin C.C., Tsai C.H. Polymorphisms for interleukin 1 beta exon 5 and interleukin 1 receptor antagonist in Taiwanese children with febrile convulsions. Arch Pediatr Adolesc Med. 2002;156:545–548. doi: 10.1001/archpedi.156.6.545. [DOI] [PubMed] [Google Scholar]
  • [21].Chou I.C., Lin W.D., Wang C.H., Tsai C.H., Li T.C., Tsai F.J. Interleukin (IL)-1beta, IL-1 receptor antagonist, IL-6, IL-8, IL-10, and tumor necrosis factor alpha gene polymorphisms in patients with febrile seizures. J Clin Lab Anal. 2010;24:154–159. doi: 10.1002/jcla.20374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22].Haspolat S., Baysal Y., Duman O., Coskun M., Tosun O., Yegin O. Interleukin-1alpha, interleukin-1beta, and interleukin-1Ra polymorphisms in febrile seizures. J Child Neurol. 2005;20:565–568. doi: 10.1177/08830738050200070401. [DOI] [PubMed] [Google Scholar]
  • [23].Serdaroğlu G., Alpman A., Tosun A., Pehlivan S., Özkinay F., Tekgul H., et al. Febrile seizures: interleukin 1beta and interleukin-1 receptor antagonist polymorphisms. Pediatr Neurol. 2009;40:113–116. doi: 10.1016/j.pediatrneurol.2008.10.004. [DOI] [PubMed] [Google Scholar]
  • [24].Helminen M., Vesikari T. Increased interleukin-1 (IL-1) production from LPS-stimulated peripheral blood monocytes in children with febrile convulsions. Acta Paediatr Scand. 1990;79:810–816. doi: 10.1111/j.1651-2227.1990.tb11559.x. [DOI] [PubMed] [Google Scholar]
  • [25].Tütüncüoğlu S., Kutukculer N., Kepe L., Coker C., Berdeli A., Tekgul H. Proinflammatory cytokines, prostaglandins and zinc in febrile convulsions. Pediatr Int. 2001;43:235–239. doi: 10.1046/j.1442-200x.2001.01389.x. [DOI] [PubMed] [Google Scholar]
  • [26].Heida J.G., Pittman Q.J. Causal links between brain cytokines and experimental febrile convulsions in the rat. Epilepsia. 2005;46:1906–1913. doi: 10.1111/j.1528-1167.2005.00294.x. [DOI] [PubMed] [Google Scholar]
  • [27].Lahat E., Livne M., Barr J., Katz Y. Interleukin-1beta levels in serum and cerebrospinal fluid of children with febrile seizures. Pediatr Neurol. 1997;17:34–36. doi: 10.1016/S0887-8994(97)00034-9. [DOI] [PubMed] [Google Scholar]
  • [28].Virta M., Hurme M., Helminen M. Increased plasma levels of proand anti-inflammatory cytokines in patients with febrile seizures. Epilepsia. 2002;43:920–923. doi: 10.1046/j.1528-1157.2002.02002.x. [DOI] [PubMed] [Google Scholar]
  • [29].Dinarello C.A. Biologic basis for interleukin-1 in disease. Blood. 1996;87:2095–2147. [PubMed] [Google Scholar]
  • [30].Cunningham A.J., Murray C.A., O’Neill L.A., Lynch M.A., O’Connor J.J. Interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro. Neurosci Lett. 1996;203:17–20. doi: 10.1016/0304-3940(95)12252-4. [DOI] [PubMed] [Google Scholar]
  • [31].Katsuki H., Nakai S., Hirai Y., Akaji K., Kiso Y., Satoh M. Interleukin-1 beta inhibits long-term potentiation in the CA3 region of mouse hippocampal slices. Eur J Pharmacol. 1990;181:323–326. doi: 10.1016/0014-2999(90)90099-R. [DOI] [PubMed] [Google Scholar]
  • [32].Schneider H., Pitossi F., Balschun D., Wagner A., del Rey A., Besedovsky H.O. A neuromodulatory role of interleukin-1beta in the hippocampus. Proc Natl Acad Sci U S A. 1998;95:7778–7783. doi: 10.1073/pnas.95.13.7778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [33].Yoshioka M., Itoh Y., Mori K., Ueno K., Matsumoto M., Togashi H. Effects of an interleukin-1beta analogue [Lys-D-Pro-Thr], on incomplete cerebral ischemia-induced inhibition of long-term potentiation in rat hippocampal neurons in vivo. Neurosci Lett. 1999;261:171–174. doi: 10.1016/S0304-3940(99)00004-X. [DOI] [PubMed] [Google Scholar]
  • [34].Dube C., Vezzani A., Behrens M., Bartfai T., Baram T.Z. Interleukin-1beta contributes to the generation of experimental febrile seizures. Ann Neurol. 2005;57:152–155. doi: 10.1002/ana.20358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [35].Vezzani A., Moneta D., Conti M., Richichi C., Ravizza T., De Luigi A., et al. Powerful anticonvulsant action of IL-1 receptor antagonist on intracerebral injection and astrocytic overexpression in mice. Proc Natl Acad Sci U S A. 2000;97:11534–11539. doi: 10.1073/pnas.190206797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [36].Heida J.G., Moshe S.L., Pittman Q.J. The role of interleukin-1beta in febrile seizures. Brain Dev. 2009;31:388–393. doi: 10.1016/j.braindev.2008.11.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [37].Sayyah M., Beheshti S., Shokrgozar M.A., Eslami-far A., Deljoo Z., Khabiri A.R., et al. Antiepileptogenic and anticonvulsant activity of interleukin-1 beta in amygdala-kindled rats. Exp Neurol. 2005;191:145–153. doi: 10.1016/j.expneurol.2004.08.032. [DOI] [PubMed] [Google Scholar]
  • [38].Plata-Salaman C.R., Ffrench-Mullen J.M. Interleukin-1 beta depresses calcium currents in CA1 hippocampal neurons at pathophysiological concentrations. Brain Res Bull. 1992;29:221–223. doi: 10.1016/0361-9230(92)90029-W. [DOI] [PubMed] [Google Scholar]
  • [39].Plata-Salaman C.R., Ffrench-Mullen J.M. Interleukin-1 beta inhibits Ca2+ channel currents in hippocampal neurons through protein kinase C. Eur J Pharmacol. 1994;266:1–10. doi: 10.1016/0922-4106(94)90202-X. [DOI] [PubMed] [Google Scholar]
  • [40].Zhou C., Ye H.H., Wang S.Q., Chai Z. Interleukin-1beta regulation of N-type Ca2+ channels in cortical neurons. Neurosci Lett. 2006;403:181–185. doi: 10.1016/j.neulet.2006.04.043. [DOI] [PubMed] [Google Scholar]
  • [41].Qi C., Zhang W.W., Li X.N., Zhou C. Interleukin-1beta inhibits the amplitudes of voltage-gated Na+ currents and action potential in cultured cortical neurons of rat. Acta Physiol Sin. 2011;63:131–137. [PubMed] [Google Scholar]
  • [42].Qi C., Zhang W.W., Wang F., Bao C.F., Wang X.W., Li X.N., et al. Acute effects of IL-1beta on sodium current in cortical neurons of rats. Zoolog Res. 2011;32:323–328. doi: 10.3724/SP.J.1141.2011.03323. [DOI] [PubMed] [Google Scholar]
  • [43].Zhang R., Yamada J., Hayashi Y., Wu Z., Koyama S., Nakanishi H. Inhibition of NMDA-induced outward currents by interleukin-1beta in hippocampal neurons. Biochem Biophys Res Commun. 2008;372:816–820. doi: 10.1016/j.bbrc.2008.05.128. [DOI] [PubMed] [Google Scholar]
  • [44].Zhang R., Sun L., Hayashi Y., Liu X., Koyama S., Wu Z., et al. Acute p38-mediated inhibition of NMDA-induced outward currents in hippocampal CA1 neurons by interleukin-1beta. Neurobiol Dis. 2010;38:68–77. doi: 10.1016/j.nbd.2009.12.028. [DOI] [PubMed] [Google Scholar]
  • [45].Lai A.Y., Swayze R.D., El-Husseini A., Song C. Interleukin-1 beta modulates AMPA receptor expression and phosphorylation in hippocampal neurons. J Neuroimmunol. 2006;175:97–106. doi: 10.1016/j.jneuroim.2006.03.001. [DOI] [PubMed] [Google Scholar]
  • [46].Yang S., Liu Z.W., Wen L., Qiao H.F., Zhou W.X., Zhang Y.X. Interleukin-1beta enhances NMDA receptor-mediated current but inhibits excitatory synaptic transmission. Brain Res. 2005;1034:172–179. doi: 10.1016/j.brainres.2004.11.018. [DOI] [PubMed] [Google Scholar]
  • [47].Viviani B., Bartesaghi S., Gardoni F., Vezzani A., Behrens M.M., Bartfai T., et al. Interleukin-1beta enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci. 2003;23:8692–8700. doi: 10.1523/JNEUROSCI.23-25-08692.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [48].Wang S., Cheng Q., Malik S., Yang J. Interleukin-1beta inhibits gamma-aminobutyric acid type A (GABA(A)) receptor current in cultured hippocampal neurons. J Pharmacol Exp Ther. 2000;292:497–504. [PubMed] [Google Scholar]
  • [49].Chou I.C., Peng C.T., Huang C.C., Tsai J.J., Tsai F.J., Tsai C.H. Association analysis of gamma 2 subunit of gamma-aminobutyric acid type A receptor polymorphisms with febrile seizures. Pediatr Res. 2003;54:26–29. doi: 10.1203/01.PDR.0000069696.96041.34. [DOI] [PubMed] [Google Scholar]
  • [50].Chou I.C., Lee C.C., Huang C.C., Wu J.Y., Tsai J.J., Tsai C.H., et al. As sociation of the neuronal nicotinic acetylcholine receptor subunit alpha4 polymorphisms with febrile convulsions. Epilepsia. 2003;44:1089–1093. doi: 10.1046/j.1528-1157.2003.t01-1-44702.x. [DOI] [PubMed] [Google Scholar]
  • [51].Peng C.T., Chou I.C., Li C.I., Hsu Y.A., Tsai C.H., Tsai F.J. Association of the nicotinic receptor beta 2 subunit and febrile seizures. Pediatr Neurol. 2004;30:186–189. doi: 10.1016/j.pediatrneurol.2003.08.001. [DOI] [PubMed] [Google Scholar]
  • [52].De Simoni M.G., Perego C., Ravizza T., Moneta D., Conti M., Marchesi F., et al. Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur J Neurosci. 2000;12:2623–2633. doi: 10.1046/j.1460-9568.2000.00140.x. [DOI] [PubMed] [Google Scholar]
  • [53].Furukawa K., Mattson M.P. The transcription factor NF-kappaB mediates increases in calcium currents and decreases in NMDA-and AMPA/kainate-induced currents induced by tumor necrosis factoralpha in hippocampal neurons. J Neurochem. 1998;70:1876–1886. doi: 10.1046/j.1471-4159.1998.70051876.x. [DOI] [PubMed] [Google Scholar]
  • [54].De A., Krueger J.M., Simasko S.M. Tumor necrosis factor alpha increases cytosolic calcium responses to AMPA and KCl in primary cultures of rat hippocampal neurons. Brain Res. 2003;981:133–142. doi: 10.1016/S0006-8993(03)02997-4. [DOI] [PubMed] [Google Scholar]
  • [55].McLarnon J.G., Franciosi S., Wang X., Bae J.H., Choi H.B., Kim S.U. Acute actions of tumor necrosis factor-alpha on intracellular Ca2+ and K+ currents in human microglia. Neuroscience. 2001;104:1175–1184. doi: 10.1016/S0306-4522(01)00119-1. [DOI] [PubMed] [Google Scholar]
  • [56].Beattie E.C., Stellwagen D., Morishita W., Bresnahan J.C., Ha B.K., Von Zastrow M., et al. Control of synaptic strength by glial TNF alpha. Science. 2002;295:2282–2285. doi: 10.1126/science.1067859. [DOI] [PubMed] [Google Scholar]
  • [57].Yu Z., Cheng G., Wen X., Wu G.D., Lee W.T., Pleasure D. Tumor necrosis factor alpha increases neuronal vulnerability to excitotoxic necrosis by inducing expression of the AMPA-glutamate receptor subunit GluR1 via an acid sphingomyelinase- and NF-kappaBdependent mechanism. Neurobiol Dis. 2002;11:199–213. doi: 10.1006/nbdi.2002.0530. [DOI] [PubMed] [Google Scholar]
  • [58].Riazi K., Galic M.A., Kuzmiski J.B., Ho W., Sharkey K.A., Pittman Q.J. Microglial activation and TNF alpha production mediate altered CNS excitability following peripheral inflammation. Proc Natl Acad Sci U S A. 2008;105:17151–17156. doi: 10.1073/pnas.0806682105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [59].Stellwagen D., Beattie E.C., Seo J.Y., Malenka R.C. Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. J Neurosci. 2005;25:3219–3228. doi: 10.1523/JNEUROSCI.4486-04.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [60].Fukuda M., Morimoto T., Suzuki Y., Shinonaga C., Ishida Y. Interleukin-6 attenuates hyperthermia-induced seizures in developing rats. Brain Dev. 2007;29:644–648. doi: 10.1016/j.braindev.2007.04.007. [DOI] [PubMed] [Google Scholar]
  • [61].Straussberg R., Amir J., Harel L., Punsky I., Bessler H. Pro- and anti-inflammatory cytokines in children with febrile convulsions. Pediatr Neurol. 2001;24:49–53. doi: 10.1016/S0887-8994(00)00234-4. [DOI] [PubMed] [Google Scholar]
  • [62].Ishizaki Y., Kira R., Fukuda M., Torisu H., Sakai Y., Sanefuji M., et al. Interleukin-10 is associated with resistance to febrile seizures: genetic association and experimental animal studies. Epilepsia. 2009;50:761–767. doi: 10.1111/j.1528-1167.2008.01861.x. [DOI] [PubMed] [Google Scholar]
  • [63].Aurelius E., Andersson B., Forsgren M., Skoldenberg B., Strannegard O. Cytokines and other markers of intrathecal immune response in patients with herpes simplex encephalitis. J Infect Dis. 1994;170:678–681. doi: 10.1093/infdis/170.3.678. [DOI] [PubMed] [Google Scholar]
  • [64].Mustafa M.M., Ramilo O., Saez-Llorens X., Olsen K.D., Magness R.R., McCracken G.H., Jr. Cerebrospinal fluid prostaglandins, interleukin 1 beta, and tumor necrosis factor in bacterial meningitis. Clinical and laboratory correlations in placebo-treated and dexamethasone-treated patients. Am J Dis Child. 1990;144:883–887. doi: 10.1001/archpedi.1990.02150320047024. [DOI] [PubMed] [Google Scholar]
  • [65].Vitkovic L., Bockaert J., Jacque C. “Inflammatory” cytokines: neuromodulators in normal brain? J Neurochem. 2000;74:457–471. doi: 10.1046/j.1471-4159.2000.740457.x. [DOI] [PubMed] [Google Scholar]
  • [66].Stoll G., Jander S., Schroeter M. Cytokines in CNS disorders: neurotoxicity versus neuroprotection. J Neural Transm Suppl. 2000;59:81–89. doi: 10.1007/978-3-7091-6781-6_11. [DOI] [PubMed] [Google Scholar]
  • [67].Gibson H.E., Edwards J.G., Page R.S., Van Hook M.J., Kauer J.A. TRPV1 channels mediate long-term depression at synapses on hippocampal interneurons. Neuron. 2008;57:746–759. doi: 10.1016/j.neuron.2007.12.027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [68].Atherton J.F., Kitano K., Baufreton J., Fan K., Wokosin D., Tkatch T., et al. Selective participation of somatodendritic HCN channels in inhibitory but not excitatory synaptic integration in neurons of the subthalamic nucleus. J Neurosci. 2010;30:16025–16040. doi: 10.1523/JNEUROSCI.3898-10.2010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [69].Obreja O., Rathee P.K., Lips K.S., Distler C., Kress M. IL-1 beta potentiates heat-activated currents in rat sensory neurons: involvement of IL-1RI, tyrosine kinase, and protein kinase C. FASEB J. 2002;16:1497–1503. doi: 10.1096/fj.02-0101com. [DOI] [PubMed] [Google Scholar]
  • [70].Fu M., Xie Z., Zuo H. TRPV1: a potential target for antiepileptogenesis. Med Hypotheses. 2009;73:100–102. doi: 10.1016/j.mehy.2009.01.005. [DOI] [PubMed] [Google Scholar]
  • [71].Baruscotti M., Bottelli G., Milanesi R., DiFrancesco J.C., DiFrancesco D. HCN-related channelopathies. Pflugers Arch. 2010;460:405–415. doi: 10.1007/s00424-010-0810-8. [DOI] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES