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. 2007 May 1;7(2):127–140. doi: 10.1111/j.1582-4934.2003.tb00211.x

Inflammatory mechanisms associated with brain damage induced by kainic acid with special reference to the interleukin‐1 system

M Oprica 1,✉, C Eriksson 2, M Schultzberg 1
PMCID: PMC6740282  PMID: 12927051

Abstract

The evidence of inflammatory processes in the clinical manifestations and neuropathological sequelae of epilepsy have accumulated in the last decade. Administration of kainic acid, an analogue of the excitatory amino acid glutamate, induces a characteristic behavioural syndrome and a reproducible pattern of neurodegeneration in several brain areas, closely resembling human temporal lobe epilepsy. Results from studies using the kainic acid model indicate that manipulation of pro‐ and anti‐inflammatory cytokines can modify the outcome with regard to the behavioural syndrome as well as the neuropathological consequences. Interleukin‐1 is one of the most important cytokines and has several actions in the brain that are critical for the host defense against injury and infection, and it is involved in the initiation of early stages of inflammation. It is believed that interleukin‐1 plays a pivotal role in the neuroinflammation associated with certain forms of neurodegeneration, including cerebral ischemia, trauma and excitotoxic brain injury. In this review, we have summarized the experimental data available with regard to the involvement of the interleukin‐1 system in kainic acid‐induced changes in the brain and emphasized the modulatory role of interleukin‐1β in this model of epilepsy.

Keywords: cytokines, excitotoxicity, epilepsy, neurodegeneration, interleukin‐1, kainic acid

References

  • 1. 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., 95: 7778–7783, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Opp M.R., Krueger J.M., Interleukin 1‐receptor antagonist blocks interleukin 1‐induced sleep and fever, Am. J. Physiol., 260: R453–457, 1991. [DOI] [PubMed] [Google Scholar]
  • 3. Berkenbosch F., van Oers J., del Rey A., Tilders F., Besedovsky H., Corticotropin‐releasing factor‐producing neurons in the rat activated by interleukin‐1, Science, 238: 524–526, 1987. [DOI] [PubMed] [Google Scholar]
  • 4. Tehranian R., Andell‐Jonsson S., Beni S.M., Yatsiv I., Shohami E., Bartfai T., Lundkvist J., Iverfeldt K., Improved recovery and delayed cytokine induction after closed head injury in mice with central overexpression of the secreted isoform of the interleukin‐1 receptor antagonist, J. Neurotrauma, 19: 939–951, 2002. [DOI] [PubMed] [Google Scholar]
  • 5. Loddick S.A., Wong M.L., Bongiorno P.B., Gold P.W., Licinio J., Rothwell NJ., Endogenous interleukin‐1 receptor antagonist is neuroprotective, Biochem. Biophys. Res. Commun., 234: 211–215, 1997. [DOI] [PubMed] [Google Scholar]
  • 6. Lawrence C.B., Allan S.M., Rothwell N.J., Interleukin‐ 1beta and the interleukin‐1 receptor antagonist act in the striatum to modify excitotoxic brain damage in the rat, Eur. J. Neurosci., 10: 1188–1195, 1998. [DOI] [PubMed] [Google Scholar]
  • 7. Holmes C., El‐Okl M., Williams A.L., Cunningham C., Wilcockson D., Perry V.H., Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease, J. Neurol. Neurosurg. Psychiatry, 74: 788–789, 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Vezzani A., Moneta D., Richichi C., Aliprandi M., Burrows S.J., Ravizza T., Perego C., De Simoni M.G., Functional role of inflammatory cytokines and antiinflammatory molecules in seizures and epileptogenesis, Epilepsia, 43: 30–35, 2002. [DOI] [PubMed] [Google Scholar]
  • 9. Vezzani A., Conti M., De Luigi A., Ravizza T., Moneta D., Marchesi F., De Simoni M.G., Interleukin–1beta immunoreactivity and microglia are enhanced in the rat hippocampus by focal kainate application: functional evidence for enhancement of electrographic seizures, Neuroscience, 19: 5054–5065, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Minami M., Kuraishi Y., Yamaguchi T., Nakai S., Hirai Y., Satoh M., Convulsants induce interleukin‐1 beta messenger RNA in rat brain, Biochem. Biophys. Res. Commun., 171: 832–837, 1990. [DOI] [PubMed] [Google Scholar]
  • 11. Eriksson C., Tehranian R., Iverfeldt K., Winblad B., Schultzberg M., Increased expression of mRNA encoding interleukin‐1β and caspase‐1, and the secreted isoform of interleukin‐1β receptor antagonist in the rat brain following systemic kainic acid administration, J. Neurosci. Res., 60: 266–279, 2000. [DOI] [PubMed] [Google Scholar]
  • 12. Anisman H., Merali Z., Cytokines, stress, and depressive illness, Brain Behav. Immun., 16: 513–524, 2002. [DOI] [PubMed] [Google Scholar]
  • 13. Aarli J.A., Epilepsy and the immune system, Arch. Neurol., 57: 1689–1692, 2000. [DOI] [PubMed] [Google Scholar]
  • 14. Peltola J., Hurme M., Miettinen A., Keranen T., Elevated levels of interleukin‐6 may occur in cerebrospinal fluid from patients with recent epileptic seizures, Epilepsy Res., 31: 129–133, 1998. [DOI] [PubMed] [Google Scholar]
  • 15. Haspolat S., Mihci E., Coskun M., Gumuslu S., Ozben T., Yegin O., Ozbenm T., Interleukin–1beta, tumor necrosis factor‐alpha, and nitrite levels in febrile seizures, J. Child Neurol., 17: 749–751, 2002. [DOI] [PubMed] [Google Scholar]
  • 16. Peltola J., Palmio J., Korhonen L., Suhonen J., Miettinen A. Hurme M., Lindholm D., Keranen T., Interleukin‐6 and interleukin‐1 receptor antagonist in cerebrospinal fluid from patients with recent tonic‐clonic seizures, Epilepsy Res., 41: 205–211, 2000. [DOI] [PubMed] [Google Scholar]
  • 17. Ben‐Ari Y., Tremblay E., Ottersen O.P., Injections of KA into the amygdaloid complex of the rat: an electrographic, clinical and histological study in relation to the pathology of epilepsy, Neuroscience, 5: 515–528, 1980. [DOI] [PubMed] [Google Scholar]
  • 18. Nadler J.V., Kainic acid as a tool for the study of temporal lobe epilepsy, Life Sci., 29: 2031–2042, 1981. [DOI] [PubMed] [Google Scholar]
  • 19. Olney J.W., Rhee V., Ho O.L., Kainic acid: a powerful neurotoxic analogue of glutamate, Brain Res., 177: 507–512, 1974. [DOI] [PubMed] [Google Scholar]
  • 20. Ozawa S., Kamiya H., Tsuzuki K., Glutamate receptors in the mammalian central nervous system, Prog. Neurobiol., 54: 581–618, 1998. [DOI] [PubMed] [Google Scholar]
  • 21. Ben‐Ari Y., Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy, Neuroscience, 14: 375–403, 1985. [DOI] [PubMed] [Google Scholar]
  • 22. Zagrean L., Varlas V., Oprica M., Munteanu A.M., Oltenschi C., Voicu T., EEG study of kainate‐induced epilepsy in non‐anaesthetized freely moving rats, Rom. J. Physiol., 30: 115–118, 1993. [PubMed] [Google Scholar]
  • 23. Turski L., Kleinrok Z., Effects of kainic acid on body temperature of rats: role of catecholaminergic and serotonergic systems, Psychopharmacology, 71: 35–39, 1980. [DOI] [PubMed] [Google Scholar]
  • 24. Oprica M., Forslin Aronsson Å., Post C., Eriksson C., Ahlenius S., Popescu L.M., Schultzberg M., Effects of alpha‐MSH on kainic acid induced changes in core temperature in rats, Peptides, 23: 143–149, 2002. [DOI] [PubMed] [Google Scholar]
  • 25. Ahlenius S., Oprica M., Eriksson C., Winblad B., Schultzberg M., Effects of kainic acid on rat body temperature: unmasking by dizocilpine, Neuropharmacology, 43: 28–35, 2002. [DOI] [PubMed] [Google Scholar]
  • 26. Sperk G., Kainic acid seizures in the rat, Prog. Neurobiol., 42: 1–32, 1994. [DOI] [PubMed] [Google Scholar]
  • 27. Coyle J.T., Neurotoxic action of kainic acid, J. Neurochem., 41: 1–11, 1983. [DOI] [PubMed] [Google Scholar]
  • 28. Sperk G., Lassmann H., Baran H., Seitelberger F., Hornykiewicz O., Kainic acid‐induced seizures: doserelationship of behavioral, neurochemical and histopathological changes, Brain Res., 338: 289–295, 1985. [DOI] [PubMed] [Google Scholar]
  • 29. Tauck D.L., Nadler J.V., Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid‐treated rats, J. Neurosci., 5: 1016–1022, 1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Phelps S., Mitchell J., Wheal H.V., Changes to synaptic ultrastructure in field CA1 of the rat hippocampus following intracerebroventricular injection of kainic acid, Neuroscience, 40: 687–699, 1991. [DOI] [PubMed] [Google Scholar]
  • 31. Tremblay E., Ottersen O.P., Rovira C., Ben‐Ari Y., Intraamygdaloid injections of kainic acid: regional metabolic changes and their relation to the pathological alterations, Neuroscience, 8: 299–315, 1983. [DOI] [PubMed] [Google Scholar]
  • 32. Tanaka T., Tanaka S., Fujita T., Takano K., Fukuda H., Sako K., Yonemasu Y., Experimental complex partial seizures induced by a microinjection of kainic acid into limbic structures, Prog. Neurobiol., 38: 317–334, 1992. [DOI] [PubMed] [Google Scholar]
  • 33. Ferrer I., Martin F., Serrano T., Reiriz J., Perez‐Navarro E., Alberch J., Macaya A., Planas A.M., Both apoptosis and necrosis occur following intrastriatal administration of excitotoxins, Acta Neuropathol., 90: 504–510, 1995. [DOI] [PubMed] [Google Scholar]
  • 34. Simonian N.A., Getz R.L., Leveque J.C., Konradi C., Coyle J.T., Kainic acid induces apoptosis in neurons, Neuroscience, 75: 1047–1055, 1996. [DOI] [PubMed] [Google Scholar]
  • 35. Popescu B.O., Oprica M., Sajin M., Stanciu C.L., Bajenaru O., Predescu A., Vidulescu C., Popescu L.M., Dantrolene protects neurons against kainic acid induced apoptosis in vitro and in vivo, J. Cell. Mol. Med., 6: 555–569, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. Krnjevic K., Morris M.E., Reiffenstein R.J., Changes in extracellular Ca2+ and K+ activity accompanying hippocampal discharges, Can. J. Physiol. Pharmacol., 58: 579–582, 1980. [DOI] [PubMed] [Google Scholar]
  • 37. Ferkany J.W., Zaczek R., Coyle J.T., Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors, Nature, 298: 757–759, 1982. [DOI] [PubMed] [Google Scholar]
  • 38. Köhler C., Schwarcz R., Fuxe K., Intrahippocampal injections of ibotenic acid provide histological evidence for a neurotoxic mechanism different from kainic acid, Neurosci. Lett., 15: 223–228, 1979. [DOI] [PubMed] [Google Scholar]
  • 39. Racine R.J., Modification of seizure activity by electrical stimulation. II. Motor seizure, Electroencephalogr. Clin. Neurophysiol., 32: 281–294, 1972. [DOI] [PubMed] [Google Scholar]
  • 40. Mosley B., Urdal D.L., Prickett K.S., Larsen A., Cosman D., Conlon P.J., Gillis S., Dower S.K., The interleukin‐1 receptor binds the human interleukin‐1 alpha precursor but not the interleukin‐1 beta precursor, J. Biol. Chem., 262: 2941–2944, 1987. [PubMed] [Google Scholar]
  • 41. Kobayashi Y., Yamamoto K., Saido T., Kawasaki H., Oppenheim J.J., Matsushima K., Identification of calcium‐activated neutral protease as a processing enzyme of human interleukin‐1 alpha, Proc. Natl. Acad. Sci., 87: 5548–5552, 1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42. Black R.A., Kronheim S.R., Cantrell M., Deeley M.C., March C.J., Prickett K.S., Wignall J., Conlon P.J., Cosman D., Hopp T.P., Generation of biologically active interleukin‐1 beta by proteolytic cleavage of the inactive precursor, J. Biol. Chem., 263: 9437–9442, 1988. [PubMed] [Google Scholar]
  • 43. Katsuura G., Gottschall P.E., Dahl R.R., Arimura A., Interleukin‐1 beta increases prostaglandin E2 in rat astrocyte cultures: modulatory effect of neuropeptides, Endocrinology, 124: 3125–3127, 1989. [DOI] [PubMed] [Google Scholar]
  • 44. Vitkovic L., Bockaert J., Jacque C., “Inflammatory” cytokines: neuromodulators in normal brain?, J. Neurochem., 74: 457–471, 2000. [DOI] [PubMed] [Google Scholar]
  • 45. Minami M., Kuraishi Y., Satoh M., Effects of kainic acid on messenger RNA levels of IL‐1 beta, IL‐6, TNF alpha and LIF in the rat brain, Biochem. Biophys. Res. Commun., 176: 593–598, 1991. [DOI] [PubMed] [Google Scholar]
  • 46. Yabuuchi K., Minami M., Katsumata S., Satoh M., In situ hybridization study of interleukin‐1 beta mRNA induced by kainic acid in the rat brain, Mol. Brain. Res., 20: 153–161, 1993. [DOI] [PubMed] [Google Scholar]
  • 47. Eriksson C., van Dam A‐M., Lucassen P.J., Bol J.G.J.M., Winblad B., Schultzberg M., Immunohistochemical localization of interleukin–1β, interleukin‐1 receptor antagonist and interleukin‐1β converting enzyme/caspase‐1 in the rat brain after peripheral administration of kainic acid, Neuroscience, 93: 915–930, 1999. [DOI] [PubMed] [Google Scholar]
  • 48. Giulian D., Baker T.J., Shih L.C., Lachman L.B., Interleukin 1 of the central nervous system is produced by ameboid microglia, J. Exp. Med., 164: 594–604, 1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49. Herx L.M., Yong V.W., Interleukin‐1 beta is required for the early evolution of reactive astrogliosis following CNS lesion, J. Neuropathol. Exp. Neurol., 60: 961–971, 2001. [DOI] [PubMed] [Google Scholar]
  • 50. Eriksson C., Zou L.P., Ahlenius S., Winblad B., Schultzberg M., Inhibition of kainic acid induced expression of interleukin‐1β and interleukin‐1 receptor antagonist mRNA in the rat brain by NMDA receptor antagonists, Mol. Brain Res., 85: 103–113, 2000. [DOI] [PubMed] [Google Scholar]
  • 51. Noda M., Nakanishi H., Nabekura J., Akaike N., AMPA‐kainate subtypes of glutamate receptor in rat cerebral microglia, J. Neurosci., 20: 251–258, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52. Dinkel K., MacPherson A., Sapolsky R.M., Novel glucocorticoid effects on acute inflammation in the CNS, J. Neurochem., 84: 705–716, 2003. [DOI] [PubMed] [Google Scholar]
  • 53. Ye Z.C., Sontheimer H., Cytokine modulation of glial glutamate uptake: a possible involvement of nitric oxide, Neuroreport, 7: 2181–2185, 1996. [DOI] [PubMed] [Google Scholar]
  • 54. Hu S., Sheng W.S., Ehrlich L.C., Peterson P.K., Chao C.C., Cytokine effects on glutamate uptake by human astrocytes, Neuroimmunomodulation, 7: 153–159, 2000. [DOI] [PubMed] [Google Scholar]
  • 55. Casamenti F., Prosperi C., Scali C., Giovannelli L., Colivicchi M.A., Faussone‐Pellegrini M.S., Pepeu G.,Interleukin‐1beta activates forebrain glial cells and increases nitric oxide production and cortical glutamate and GABA release in vivo: implications for Alzheimer's disease, Neuroscience, 91: 831–842, 1999. [DOI] [PubMed] [Google Scholar]
  • 56. Hewett S.J., Csernansky C.A., Choi D.W., Selective potentiation of NMDA‐induced neuronal injury following induction of astrocytic iNOS, Neuron, 13: 487–494, 1994. [DOI] [PubMed] [Google Scholar]
  • 57. Vincent V.A., Tilders F.J., van Dam A.M., Inhibition of endotoxin‐induced nitric oxide synthase production in microglial cells by the presence of astroglial cells: a role for transforming growth factor beta, Glia, 19: 190–198, 1997. [DOI] [PubMed] [Google Scholar]
  • 58. Schubert P., Morino T., Miyazaki H., Ogata T., Nakamura Y., Marchini C., Ferroni S., Cascading glia reactions: a common pathomechanism and its differentiated control by cyclic nucleotide signaling, Ann. N. Y. Acad. Sci., 903: 24–33, 2000. [DOI] [PubMed] [Google Scholar]
  • 59. Liu Z., Gatt A., Mikati M., Holmes G. L., Effect of temperature on kainic acid‐induced seizures, Brain Res., 631: 51–58, 1993. [DOI] [PubMed] [Google Scholar]
  • 60. Maeda T., Hashizume K., Tanaka T., Effect of hypothermia on KA‐induced limbic seizures: an electroencephalographic and 14C‐deoxyglucose autoradiographic study, Brain Res., 818: 228–235, 1999. [DOI] [PubMed] [Google Scholar]
  • 61. Lawrence C.B., Allan S.M., Rothwell N.J., Interleukin‐1beta and the interleukin‐1 receptor antagonist act in the striatum to modify excitotoxic brain damage in the rat, Eur. J. Neurosci., 10: 1188–1195, 1998. [DOI] [PubMed] [Google Scholar]
  • 62. Giulian D., Young D.G., Woodward J., Brown D.C., Lachman L.B., Interleukin‐1 is an astroglial growth factor in the developing brain, J. Neurosci., 8: 709–714, 1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63. Ling Z.D., Potter E.D., Lipton J.W., Carvey P.M., Differentiation of mesencephalic progenitor cells into dopaminergic neurons by cytokines, Exp. Neurol., 149: 411–423, 1998. [DOI] [PubMed] [Google Scholar]
  • 64. Gall C., Murray K., Isackson P.J., Kainic acid‐induced seizures stimulate increased expression of nerve growth factor mRNA in rat hippocampus, Mol. Brain Res., 9: 113–123, 1991. [DOI] [PubMed] [Google Scholar]
  • 65. Strauss S., Otten U., Joggerst B., Pluss K., Volk B., Increased levels of nerve growth factor [NGF] protein and mRNA and reactive gliosis following kainic acid injection into the rat striatum, Neurosci. Lett., 168: 193–196, 1994. [DOI] [PubMed] [Google Scholar]
  • 66. Spranger M., Lindholm D., Bandtlow C., Heumann R., Gnahn H., Naher‐Noe M., Thoenen H., Regulation of Nerve Growth Factor (NGF) Synthesis in the Rat Central Nervous System: Comparison between the Effects of Interleukin‐1 and Various Growth Factors in Astrocyte Cultures and in vivo, Eur. J. Neurosci., 2: 69–76, 1990. [DOI] [PubMed] [Google Scholar]
  • 67. DeKosky S.T., Styren S.D., O'Malley M.E., Goss J.R., Kochanek P., Marion D., Evans C.H., Robbins P.D., Interleukin‐1 receptor antagonist suppresses neurotrophin response in injured rat brain, Ann. Neurol., 39: 123–127, 1996. [DOI] [PubMed] [Google Scholar]
  • 68. Gadient R.A., Cron K.C., Otten U., Interleukin‐1 beta and tumor necrosis factor‐alpha synergistically stimulate nerve growth factor [NGF] release from cultured rat astrocytes, Neurosci. Lett., 117: 335–340, 1990. [DOI] [PubMed] [Google Scholar]
  • 69. Strijbos P.J., Rothwell N.J., Interleukin‐1 beta attenuates excitatory amino acid‐induced neurodegeneration in vitro: involvement of nerve growth factor, J. Neurosci., 15: 3468–3474, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70. Herx L.M., Rivest S., Yong V.W., Central nervous system‐initiated inflammation and neurotrophism in trauma: IL‐1 beta is required for the production of ciliary neurotrophic factor, J. Immunol., 165: 2232–2239, 2000. [DOI] [PubMed] [Google Scholar]
  • 71. Murray C.A., McGahon B., McBennett S., Lynch M.A., Interleukin‐1 beta inhibits glutamate release in hippocampus of young, but not aged, rats, Neurobiol. Aging., 18: 343–348, 1997. [DOI] [PubMed] [Google Scholar]
  • 72. Miller L.G., Fahey J.M., Interleukin‐1 modulates GABAergic and glutamatergic function in brain, Ann. N. Y. Acad. Sci., 739: 292–298, 1994. [DOI] [PubMed] [Google Scholar]
  • 73. Borth W., Alpha 2‐macroglobulin, a multifunctional binding protein with targeting characteristics, FASEB J., 6: 3345–3353, 1992. [DOI] [PubMed] [Google Scholar]
  • 74. Gebicke‐Haerter P.J., Bauer J., Brenner A., Gerok W., Alpha 2‐macroglobulin synthesis in an astrocyte subpopulation, J. Neurochem., 49: 1139–1145, 1987. [DOI] [PubMed] [Google Scholar]
  • 75. Andus T., Geiger T., Hirano T., Kishimoto T., Tran‐Thi TA., Decker K., Heinrich P.C., Regulation of synthesis and secretion of major rat acute‐phase proteins by recombinant human interleukin‐6 (BSF‐2/IL‐6) in hepatocyte primary cultures, Eur. J. Biochem., 173: 287–293, 1988. [DOI] [PubMed] [Google Scholar]
  • 76. Mori T., Iijima N., Kitabatake K., Kohsaka S., Alpha 2‐ macroglobulin is an astroglia‐derived neurite‐promoting factor for cultured neurons from rat central nervous system, Brain Res., 527: 55–61, 1990. [DOI] [PubMed] [Google Scholar]
  • 77. Higuchi M., Ito T., Imai Y., Iwaki T., Hattori M., Kohsaka S., Niho Y., Sakaki Y., Expression of the alpha 2‐macroglobulin‐encoding gene in rat brain and cultured astrocytes, Gene, 141: 155–162, 1994. [DOI] [PubMed] [Google Scholar]
  • 78. Benveniste E.N., Sparacio S.M., Norris J.G., Grenett H.E., Fuller G.M., Induction and regulation of interleukin‐6 gene expression in rat astrocytes, J. Neuroimmunol., 30: 201–212, 1990. [DOI] [PubMed] [Google Scholar]
  • 79. Yasukawa K., Hirano T., Watanabe Y., Muratani K., Matsuda T., Nakai S., Kishimoto T., Structure and expression of human B cell stimulatory factor‐2 [BSF‐2/IL‐6] gene, EMBO J., 6: 2939–2945, 1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80. Penkowa M., Molinero A., Carrasco J., Hidalgo J., Interleukin‐6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid‐induced seizures, Neuroscience, 102: 805–818, 2001. [DOI] [PubMed] [Google Scholar]
  • 80. Minghetti L., Nicolini A., Polazzi E., Greco A., Perretti M., Parente L., Levi G., Down‐regulation of microglial cyclo‐oxygenase‐2 and inducible nitric oxide synthase expression by lipocortin 1, Br. J. Pharmacol., 126: 1307–1314, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81. Miyachi T., Asai K., Tsuiki H., Mizuno H., Yamamoto N., Yokoi T., Aoyama M., Togari H., Wada Y., Miura Y., Kato T., Interleukin‐1beta induces the expression of lipocortin 1 mRNA in cultured rat cortical astrocytes, Neurosci. Res., 40: 53–60, 2001. [DOI] [PubMed] [Google Scholar]
  • 82. Liao Z., Grimshaw R.S., Rosenstreich D.L., Identification of a specific interleukin 1 inhibitor in the urine of febrile patients, J. Exp. Med., 159: 126–136, 1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83. Dinarello C.A., Interleukin‐1 and interleukin‐1 antagonism, Blood, 77: 1627–1652, 1991. [PubMed] [Google Scholar]
  • 84. Eriksson C., Winblad B., Schultzberg M., Kainic acid induced expression of interleukin‐1 receptor antagonist mRNA in the rat brain, Mol. Brain Res., 58: 195–208, 1998. [DOI] [PubMed] [Google Scholar]
  • 85. Zafra F., Lindholm D., Castren E., Hartikka J., Thoenen H., Regulation of brain‐derived neurotrophic factor and nerve growth factor mRNA in primary cultures of hippocampal neurons and astrocytes, J. Neurosci., 12: 4793–4799, 1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86. Panegyres P.K., Hughes J., The neuroprotective effects of the recombinant interleukin‐1 receptor antagonist rhIL‐1ra after excitotoxic stimulation with kainic acid and its relationship to the amyloid precursor protein gene, J. Neurol. Sci., 154: 123–132, 1998. [DOI] [PubMed] [Google Scholar]
  • 87. Loddick S.A., Wong M.L., Bongiorno P.B., Gold P.W., Licinio J., Rothwell NJ., Endogenous interleukin‐1 receptor antagonist is neuroprotective, Biochem. Biophys. Res. Commun., 234: 211–215, 1997. [DOI] [PubMed] [Google Scholar]
  • 88. Yang G.Y., Zhao Y.J., Davidson B.L., Betz A.L., Overexpression of interleukin‐1 receptor antagonist in the mouse brain reduces ischemic brain injury, Brain Res., 751: 181–188, 1997. [DOI] [PubMed] [Google Scholar]
  • 89. Golden G.T., Smith G.G., Ferraro T.N., Reyes P.F., Rat strain and age differences in kainic acid induced seizures, Epilepsy Res., 20: 151–159, 1995. [DOI] [PubMed] [Google Scholar]
  • 90. Xiao E., Xia L., Ferin M., Wardlaw S.L., Intracerebroventricular injection of interleukin‐1 stimulates the release of high levels of interleukin‐6 and interleukin‐1 receptor antagonist into peripheral blood in the primate, J. Neuroimmunol., 97: 70–76, 1999. [DOI] [PubMed] [Google Scholar]
  • 91. Berg M., Bruhn T., Johansen F.F., Diemer N.H., Kainic acid‐induced seizures and brain damage in the rat: different effects of NMDA‐ and AMPA‐receptor antagonists, Pharmacol. Toxicol., 73: 262–268, 1993. [DOI] [PubMed] [Google Scholar]
  • 92. Clifford D.B., Olney J.W., Benz A.M., Fuller T.A., Zorumski C.F., Ketamine, phencyclidine, and MK‐801 protect against kainic acid‐induced seizure‐related brain damage, Epilepsia, 31: 382–390, 1990. [DOI] [PubMed] [Google Scholar]
  • 93. Friedman W.J., Cytokines regulate expression of the type 1 interleukin‐1 receptor in rat hippocampal neurons and glia, Exp. Neurol., 168: 23–31, 2001. [DOI] [PubMed] [Google Scholar]
  • 94. Yabuuchi K., Minami M., Katsumata S., Satoh M., Localization of type I interleukin‐1 receptor mRNA in the rat brain, Mol. Brain Res., 27: 27–36, 1994. [DOI] [PubMed] [Google Scholar]
  • 95. Cunningham E.T., Wada E., Carter D.B., Tracey D.E., Battey J.F., De Souza E.B., Localization of interleukin‐1 receptor messenger RNA in murine hippocampus, Endocrinology, 128: 2666–2668, 1991. [DOI] [PubMed] [Google Scholar]
  • 96. Lynch M.A., Interleukin‐1 beta exerts a myriad of effects in the brain and in particular in the hippocampus: analysis of some of these actions, Vitam. Horm., 64: 185–219, 2002. [DOI] [PubMed] [Google Scholar]
  • 97. Bankers‐Fulbright J.L., Kalli K.R., McKean D.J., Interleukin‐1 signal transduction. Life Sci., 59: 61–83, 1996. [DOI] [PubMed] [Google Scholar]
  • 98. Arend W.P., Welgus H.G., Thompson R.C., Eisenberg S.P., Biological properties of recombinant human monocyte‐derived interleukin 1 receptor antagonist, J. Clin. Invest. 85: 1694–1697, 1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 99. Ban E., Milon G., Prudhomme N., Fillion G., Haour F., Receptors for interleukin‐1 (alpha and beta) in mouse brain: mapping and neuronal localization in hippocampus, Neuroscience, 43: 21–30, 1991. [DOI] [PubMed] [Google Scholar]
  • 100. Nishiyori A., Minami M., Takami S., Satoh M., Type 2 interleukin‐1 receptor mRNA is induced by kainic acid in the rat brain, Mol. Brain. Res., 50: 237–245, 1997. [DOI] [PubMed] [Google Scholar]
  • 101. Colotta F., Re F., Muzio M., Bertini R., Polentarutti N., Sironi M., Giri J.G., Dower S.K., Sims J.E., Mantovani A., Interleukin‐1 type II receptor: a decoy target for IL‐1 that is regulated by IL‐4, Science, 261: 472–475, 1993. [DOI] [PubMed] [Google Scholar]

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