Skip to main content
SpringerLink
Log in

Kainic acid-mediated excitotoxicity as a model for neurodegeneration

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Neuronal excitation involving the excitatory glutamate receptors is recognized as an important underlying mechanism in neurodegenerative disorders. Excitation resulting from stimulation of the ionotropic glutamate receptors is known to cause the increase in intracellular calcium and trigger calcium-dependent pathways that lead to neuronal apoptosis. Kainic acid (KA) is an agonist for a subtype of ionotropic glutamate receptor, and administration of KA has been shown to increase production of reactive oxygen species, mitochondrial dysfunction, and apoptosis in neurons in many regions of the brain, particularly in the hippocampal subregions of CA1 and CA3, and in the hilus of dentate gyrus (DG). Systemic injection of KA to rats also results in activation of glial cells and inflammatory responses typically found in neurodegenerative diseases. KA-induced selective vulnerability in the hippocampal neurons is related to the distribution and selective susceptibility of the AMPA/kainate receptors in the brain. Recent studies have demonstrated ability of KA to alter a number of intracellular activities, including accumulation of lipofuscin-like substances, induction of complement proteins, processing of amyloid precursor protein, and alteration of tau protein expression. These studies suggest that KA-induced excitotoxicity can be used as a model for elucidating mechanisms underlying oxidative stress and inflammation in neurodegenerative diseases. The focus of this review is to summarize studies demonstrating KA-induced excitotoxicity in the central nervous system and possible intervention by anti-oxidants.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jellinger K.A. and Stadelmann C. (2000) Mechanisms of cell death in neurodegenerative disorders. J. Neural. Transm. 59(Suppl.), 95–114.

    CAS  Google Scholar 

  2. Doble A. (1999) The role of excitotoxicity in neurodegenerative disease: implications for therapy. Pharmacol. Ther. 81, 163–221.

    Article  PubMed  CAS  Google Scholar 

  3. Meldrum B.S. (2000) Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J. Nutr. 130, 1007S-1015S.

    PubMed  CAS  Google Scholar 

  4. Sun A.Y. and Chen Y.M. (1998) Oxidative stress and neurodegenerative disorders. J. Biomed. Sci. 5, 401–414.

    Article  PubMed  CAS  Google Scholar 

  5. Coyle J.T. (1987) Kainic acid: insights into excitatory mechanisms causing selective neuronal degeneration. Ciba Found. Symp. 126, 186–203.

    PubMed  CAS  Google Scholar 

  6. Bleakman D. and Lodge D. (1998) Neuropharmacology of AMPA and kainate receptors. Neuropharmacology 37, 1187–1204.

    Article  PubMed  CAS  Google Scholar 

  7. Sun A.Y., Cheng Y., and Sun G.Y. (1992) Kainic acid-induced excitotoxicity in neurons and glial cells. Prog. Brain Res. 94, 271–280.

    PubMed  CAS  Google Scholar 

  8. Cheng Y. and Sun A.Y. (1994) Oxidative mechanisms involved in kainate-induced cytotoxicity in cortical neurons. Neurochem. Res. 19, 1557–1564.

    Article  PubMed  CAS  Google Scholar 

  9. Gluck M.R., Jayatilleke E., Shaw S., et al. (2000) CNS oxidative stress associated with the kainic acid rodent model of experimental epilepsy. Epilepsy Res. 39, 63–71.

    Article  PubMed  CAS  Google Scholar 

  10. Milatovic D., Gupta R.C., and Dettbarn W.D. (2002) Involvement of nitric oxide in kainic acid-induced excitotoxicity in rat brain. Brain Res. 957, 330–337.

    Article  PubMed  CAS  Google Scholar 

  11. Candelario-Jalil E., Al-Dalain S.M., Castillo R., et al. (2001) Selective vulnerability to kainate-induced oxidative damage in different rat brain regions. J. Appl. Toxicol. 21, 403–407.

    Article  PubMed  CAS  Google Scholar 

  12. Dawson R., Jr., Beal M.F., Bondy S.C., et al. (1995) Excitotoxins, aging, and environmental neurotoxins: implications for understanding human neurodegenerative diseases. Toxicol. Appl. Pharmacol. 134, 1–17.

    Article  PubMed  CAS  Google Scholar 

  13. 1Berger R. and Garnier Y. (1999) Pathophysiology of perinatal brain damage. Brain Res. Brain Res. Rev. 30, 107–134.

    Article  Google Scholar 

  14. Arundine M. and Tymianski M. (2003) Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium 34, 325–337.

    Article  PubMed  CAS  Google Scholar 

  15. Arundine M. and Tymianski M. (2004) Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury. Cell. Mol. Life Sci. 61, 657–668.

    Article  PubMed  CAS  Google Scholar 

  16. Shen W., Zhang C., and Zhang G. (2002) Nuclear factor kappaB activation is mediated by NMDA and non-NMDA receptor and L-type voltage-gated Ca(2+) channel following severe global ischemia in rat hippocampus. Brain Res. 933, 23–30.

    Article  PubMed  CAS  Google Scholar 

  17. Yin H.Z., Sensi S.L., Carriedo S.G., et al. (1999) Dendritic localization of Ca(2+)-permeable AMPA/kainate channels in hippocampal pyramidal neurons. J. Comp. Neurol. 409, 250–260.

    Article  PubMed  CAS  Google Scholar 

  18. Ogoshi F. and Weiss J.H. (2003) Heterogeneity of Ca2+-permeable AMPA/kainate channel expression in hippocampal pyramidal neurons: fluorescence imaging and immunocytochemical assessment. J. Neurosci. 23, 10,521–10,530.

    CAS  Google Scholar 

  19. Grooms S.Y., Opitz T., Bennett M.V., et al. (2000) Status epilepticus decreases glutamate receptor 2 mRNA and protein expression in hippocampal pyramidal cells before neuronal death. Proc. Natl. Acad. Sci. USA 97, 3631–3636.

    Article  PubMed  CAS  Google Scholar 

  20. Li S.Y., Ni J.H., Xu D.S., et al. (2003) Down-regulation of GluR2 is associated with Ca2+-dependent protease activities in kainate-induced apoptotic cell death in cultured rat hippocampal neurons. Neurosci. Lett. 352, 105–108.

    Article  PubMed  CAS  Google Scholar 

  21. Pellegrini-Giampietro D.E., Gorter J.A., Bennett M.V., et al. (1997) The GluR2 (GluR-B) hypothesis: Ca(2+)-permeable AMPA receptors in neurological disorders. Trends Neurosci. 20, 464–470.

    Article  PubMed  CAS  Google Scholar 

  22. Friedman L.K. (1998) Selective reduction of GluR2 protein in adult hippocampal CA3 neurons following status epilepticus but prior to cell loss. Hippocampus 8, 511–525.

    Article  PubMed  CAS  Google Scholar 

  23. Weiss J.H. and Sensi S.L. (2000) Ca2+-Zn2+ permeable AMPA or kainate receptors: possible key factors in selective neurodegeneration. Trends Neurosci. 23, 365–371.

    Article  PubMed  CAS  Google Scholar 

  24. Sun A.Y., Cheng Y., Bu Q., et al. (1992) The biochemical mechanisms of the excitotoxicity of kainic acid. Free radical formation. Mol. Chem. Neuropathol. 17, 51–63.

    Article  PubMed  CAS  Google Scholar 

  25. Candelario-Jalil E. and Sonia Leon O. (2003) Effects of nimesulide on kainate-induced in vitro oxidative damage in rat brain homogenates. BMC Pharmacol. 3, 7.

    Article  PubMed  Google Scholar 

  26. Wang Q., Yu S., Simonyi A., Rottinghaus G., Sun G.Y., and Sun A.Y. (2004) Resveratrol protects against neurotoxicity induced by kainic acid. Neurochem. Res., 29, 2105–2112.

    Article  PubMed  CAS  Google Scholar 

  27. Patel M. and Li Q.Y. (2003) Age dependence of seizure-induced oxidative stress. Neuroscience 118, 431–437.

    Article  PubMed  CAS  Google Scholar 

  28. Lei D.L., Yang D.L., and Liu H.M. (1996) Local injection of kainic acid causes widespread degeneration of NADPH-d neurons and induction of NADPH-d in neurons, endothelial cells and reactive astrocytes. Brain Res. 730, 199–206.

    PubMed  CAS  Google Scholar 

  29. Yasuda H., Fujii M., Fujisawa H., et al. (2001) Changes in nitric oxide synthesis and epileptic activity in the contralateral hippocampus of rats following intrahippocampal kainate injection. Epilepsia 42, 13–20.

    Article  PubMed  CAS  Google Scholar 

  30. Brown G.C. and Borutaite V. (2001) Nitric oxide, mitochondria, and cell death. IUBMB Life 52, 189–195.

    Article  PubMed  CAS  Google Scholar 

  31. Michaelis E.K. (1998) Molecular biology of glutamate receptors in the central nervous system and their role in excitotoxicity, oxidative stress and aging. Prog. Neurobiol. 54, 369–415.

    Article  PubMed  CAS  Google Scholar 

  32. Malva J.O., Carvalho A.P., and Carvalho C.M. (1998) Kainate receptors in hippocampal CA3 subregion: evidence for a role in regulating neurotransmitter release. Neurochem. Int. 32, 1–6.

    Article  PubMed  CAS  Google Scholar 

  33. Araki T., Simon R.P., Taki W., et al. (2002) Characterization of neuronal death induced by focally evoked limbic seizures in the C57BL/6 mouse. J. Neurosci. Res. 69, 614–621.

    Article  PubMed  CAS  Google Scholar 

  34. Tomioka M., Shirotani K., Iwata N., et al. (2002) In vivo role of caspases in excitotoxic neuronal death: generation and analysis of transgenic mice expressing baculoviral caspase inhibitor, p35, in postnatal neurons. Brain Res. Mol. Brain Res. 108, 18–32.

    Article  PubMed  CAS  Google Scholar 

  35. Chen Z., Ljunggren H.G., Zhu S.W., et al. (2004) Reduced susceptibility to kainic acid-induced excitoxicity in T-cell deficient CD4/CD8(−/−) and middle-aged C57BL/6 mice. J. Neuroimmunol. 146, 33–38.

    Article  PubMed  CAS  Google Scholar 

  36. Schauwecker P.E. (2002) Modulation of cell death by mouse genotype: differential vulnerability to excitatory amino acid-induced lesions. Exp. Neurol. 178, 219–235.

    Article  PubMed  CAS  Google Scholar 

  37. Nishiyama K., Kwak S., Takekoshi S., et al. (1996) In situ nick end-labeling detects necrosis of hippocampal pyramidal cells induced by kainic acid. Neurosci. Lett. 212, 139–142.

    Article  PubMed  CAS  Google Scholar 

  38. Osaka H., McGinty A., Hoepken U.E., et al. (1999) Expression of C5a receptor in mouse brain: role in signal transduction and neurodegeneration. Neuroscience 88, 1073–1082.

    Article  PubMed  CAS  Google Scholar 

  39. Liu W., Kato M., Itoigawa M., et al. (2001) Distinct involvement of NF-kappaB and p38 mitogen-activated protein kinase pathways in serum deprivation-mediated stimulation of inducible nitric oxide synthase and its inhibition by 4-hydroxynonenal. J. Cell. Biochem. 83, 271–280.

    Article  PubMed  CAS  Google Scholar 

  40. Faherty C.J., Xanthoudakis S., and Smeyne R.J. (1999) Caspase-3-dependent neuronal death in the hippocampus following kainic acid treatment. Brain Res. Mol. Brain Res. 70, 159–163.

    Article  PubMed  CAS  Google Scholar 

  41. Aschner M. (1998) Astrocytes as mediators of immune and inflammatory responses in the CNS. Neurotoxicology 19, 269–281.

    PubMed  CAS  Google Scholar 

  42. Zhang W., Smith C., Howlett C., et al. (2000) Inflammatory activation of human brain endothelial cells by hypoxic astrocytes in vitro is mediated by IL-1beta. J. Cereb. Blood Flow Metab. 20, 967–978.

    Article  PubMed  CAS  Google Scholar 

  43. Li W., Xia J., and Sun G.Y. (1999) Cytokine induction of iNOS and sPLA2 in immortalized astrocytes (DITNC): response to genistein and pyrrolidine dithiocarbamate. J. Interferon Cytokine Res. 19, 121–127.

    Article  PubMed  Google Scholar 

  44. Calabrese V., Copani A., Testa D., et al. (2000) Nitric oxide synthase induction in astroglial cell cultures: effect on heat shock protein 70 synthesis and oxidant/antioxidant balance. J. Neurosci. Res. 60, 613–622.

    Article  PubMed  CAS  Google Scholar 

  45. Akama K.T. and Van Eldik L.J. (2000) Beta-amyloid stimulation of inducible nitric-oxide synthase in astrocytes is interleukin-1beta- and tumor necrosis factor-alpha (TNFalpha)-dependent, and involves a TNFalpha receptor-associated factor- and NFkappaB-inducing kinase-dependent signaling mechanism. J. Biol. Chem. 275, 7918–7924.

    Article  PubMed  CAS  Google Scholar 

  46. Kyrkanides S., Moore A.H., Olschowka J.A., et al. (2002) Cyclooxygenase-2 modulates brain inflammation-related gene expression in central nervous system radiation injury. Brain Res. Mol. Brain Res. 104, 159–169.

    Article  PubMed  CAS  Google Scholar 

  47. Dorandeu F., Pernot-Marino I., Veyret J., et al. (1998) Secreted phospholipase A2-induced neurotoxicity and epileptic seizures after intracerebral administration: an unexplained heterogeneity as emphasized with paradoxin and crotoxin. J. Neurosci. Res. 54, 848–862.

    Article  PubMed  CAS  Google Scholar 

  48. Wang J.H. and Sun G.Y. (2000) Platelet activating factor (PAF) antagonists on cytokine induction of iNOS and sPLA2 in immortalized astrocytes (DITNC). Neurochem. Res. 25, 613–619.

    Article  PubMed  CAS  Google Scholar 

  49. Xu J., Weng Y.I., Simonyi A., et al. (2002) Role of PKC and MAPK in cytosolic PLA2 phosphorylation and arachadonic acid release in primary murine astrocytes. J. Neurochem. 83, 259–270.

    Article  PubMed  CAS  Google Scholar 

  50. Xu J., Yu S., Sun A.Y., et al. (2003) Oxidant-mediated AA release from astrocytes involves cPLA(2) and iPLA(2). Free Radical Biol. Med. 34, 1531–1543.

    Article  CAS  Google Scholar 

  51. Farooqui A.A., Yi Ong W., Lu X.R., et al. (2001) Neurochemical consequences of kainate-induced toxicity in brain: involvement of arachidonic acid release and prevention of toxicity by phospholipase A(2) inhibitors. Brain Res. Brain Res. Rev. 38, 61–78.

    Article  PubMed  CAS  Google Scholar 

  52. Farooqui A.A., Yang H.C., Rosenberger T.A., et al. (1997) Phospholipase A2 and its role in brain tissue. J. Neurochem. 69, 889–901.

    Article  PubMed  CAS  Google Scholar 

  53. Farooqui A.A., Ong W.Y., and Horrocks L.A. (2004) Neuroprotection abilities of cytosolic phospholipase A2 inhibitors in kainic acid-induced neurodegeneration. Curr. Drug Targets Cardiovasc. Haematol. Disord. 4, 85–96.

    Article  PubMed  CAS  Google Scholar 

  54. Albers D.S. and Beal M.F. (2000) Mitochondrial dysfunction and oxidative stress in aging and neurodegenerative disease. J. Neural. Transm. 59(Suppl.), 133–154.

    CAS  Google Scholar 

  55. Kim H.C., Bing G., Jhoo W.K., et al. (2002) Oxidative damage causes formation of lipofuscin-like substances in the hippocampus of the senescence-accelerated mouse after kainate treatment. Behav. Brain Res. 131, 211–220.

    Article  PubMed  CAS  Google Scholar 

  56. Ivy G.O., Roopsingh R., Kanai S., et al. (1996) Leupeptin causes an accumulation of lipofuscin-like substances and other signs of aging in kidneys of young rats: further evidence for the protease inhibitor model of aging. Ann. NY Acad. Sci. 786, 12–23.

    Article  PubMed  CAS  Google Scholar 

  57. Asha Devi S., Prathima S., and Subramanyam M.V. (2003) Dietary vitamin E and physical exercise: II. Antioxidant status and lipofuscinlike substances in aging rat heart. Exp. Gerontol. 38, 291–297.

    Article  PubMed  CAS  Google Scholar 

  58. Maddalena A., Papassotiropoulos A., Muller-Tillmanns B., et al. (2003) Biochemical diagnosis of Alzheimer disease by measuring the cerebrospinal fluid ratio of phosphorylated tau protein to beta-amyloid peptide42. Arch. Neurol. 60, 1202–1206.

    Article  PubMed  Google Scholar 

  59. Rego A.C. and Oliveira C.R. (2003) Mitochondrial dysfunction and reactive oxygen species in excitotoxicity and apoptosis: implications for the pathogenesis of neurodegenerative diseases. Neurochem. Res. 28, 1563–1574.

    Article  PubMed  CAS  Google Scholar 

  60. Panegyres P.K. (1998) The effects of excitotoxicity on the expression of the amyloid precursor protein gene in the brain and its modulation by neuroprotective agents. J. Neural. Transm. 105, 463–478.

    Article  PubMed  CAS  Google Scholar 

  61. Shoham S. and Ebstein R.P. (1997) The distribution of beta-amyloid precursor protein in rat cortex after systemic kainate-induced seizures. Exp. Neurol. 147, 361–376.

    Article  PubMed  CAS  Google Scholar 

  62. Ong W.Y., He Y., and Garey L.J. (1997) Distribution of amyloid beta-protein immunoreactivity in the hippocampus of rats injected with kainate. J. Hirnforsch. 38, 353–361.

    PubMed  CAS  Google Scholar 

  63. Louzada P.R., Jr., Paula Lima A.C., de Mello F.G., et al. (2001) Dual role of glutamatergic neurotransmission on amyloid beta(1–42) aggregation and neurotoxicity in embryonic avian retina. Neurosci. Lett. 301, 59–63.

    Article  PubMed  CAS  Google Scholar 

  64. Morimoto K. and Oda T. (2003) Kainate exacerbates beta-amyloid toxicity in rat hippocampus. Neurosci. Lett. 340, 242–244.

    Article  PubMed  CAS  Google Scholar 

  65. Harris K.A., Oyler G.A., Doolittle G.M., et al. (1993) Okadaic acid induces hyperphosphorylated forms of tau protein in human brain slices. Ann. Neurol. 33, 77–87.

    Article  PubMed  CAS  Google Scholar 

  66. Esclaire F., Lesort M., Blanchard C., et al. (1997) Glutamate toxicity enhances tau gene expression in neuronal cultures. J. Neurosci. Res. 49, 309–318.

    Article  PubMed  CAS  Google Scholar 

  67. Hugon J., Terro F., Esclaire F., et al. (2000) Markers of apoptosis and models of programmed cell death in Alzheimer’s disease. J. Neural. Transm. 59(Suppl.), 125–131.

    CAS  Google Scholar 

  68. Esclaire F., Terro F., Yardin C., et al. (1998) Neuronal apoptosis is associated with a decrease in tau mRNA expression. Neuroreport 9, 1173–1177.

    Article  PubMed  CAS  Google Scholar 

  69. Hugon J., Esclaire F., Lesort M., et al. (1999) Toxic neuronal apoptosis and modifications of tau and APP gene and protein expressions. Drug Metab. Rev. 31, 635–647.

    Article  PubMed  CAS  Google Scholar 

  70. Verbeek M.M., Otte-Holler I., van den Born J., et al. (1999) Agrin is a major heparan sulfate proteoglycan accumulating in Alzheimer’s disease brain. Am. J. Pathol. 155, 2115–2125.

    PubMed  CAS  Google Scholar 

  71. van Horssen J., Otte-Holler I., David G., et al. (2001) Heparan sulfate proteoglycan expression in cerebrovascular amyloid beta deposits in Alzheimer’s disease and hereditary cerebral hemorrhage with amyloidosis (Dutch) brains. Acta Neuropathol. (Berl). 102, 604–614.

    Google Scholar 

  72. van Horssen J., Kleinnijenhuis J., Maass C.N., et al. (2002) Accumulation of heparan sulfate proteoglycans in cerebellar senile plaques. Neurobiol. Aging 23, 537–545.

    Article  PubMed  Google Scholar 

  73. Shee W.L., Ong W.Y., and Lim T.M. (1998) Distribution of perlecan in mouse hippocampus following intracerebroventricular kainate injections. Brain Res. 799, 292–300.

    Article  PubMed  CAS  Google Scholar 

  74. Yasojima K., Schwab C., McGeer E.G., et al. (1999) Up-regulated production and activation of the complement system in Alzheimer’s disease brain. Am. J. Pathol. 154, 927–936.

    PubMed  CAS  Google Scholar 

  75. Lynch N.J., Willis C.L., Nolan C.C., et al. (2004) Microglial activation and increased synthesis of complement component C1q precedes blood-brain barrier dysfunction in rats. Mol. Immunol. 40, 709–716.

    Article  PubMed  CAS  Google Scholar 

  76. Fonseca M.I., Kawas C.H., Troncoso J.C., et al. (2004) Neuronal localization of C1q in preclinical Alzheimer’s disease. Neurobiol. Dis. 15, 40–46.

    Article  PubMed  CAS  Google Scholar 

  77. Fan R. and Tenner A.J. (2004) Complement C1q expression induced by Abeta in rat hippocampal organotypic slice cultures. Exp. Neurol. 185, 241–253.

    Article  PubMed  CAS  Google Scholar 

  78. Sarvari M., Vago I., Weber C.S., et al. (2003) Inhibition of C1q-beta-amyloid binding protects hippocampal cells against complement mediated toxicity. J. Neuroimmunol. 137, 12–18.

    Article  PubMed  CAS  Google Scholar 

  79. Goldsmith S.K., Wals P., Rozovsky I., et al. (1997) Kainic acid and decorticating lesions stimulate the synthesis of C1q protein in adult rat brain. J. Neurochem. 68, 2046–2052.

    Article  PubMed  CAS  Google Scholar 

  80. Miller N.J. and Rice-Evans C.A. (1995) Antioxidant activity of resveratrol in red wine. Clin. Chem. 41, 1789.

    PubMed  CAS  Google Scholar 

  81. Fremont L. (2000) Biological effects of resveratrol. Life Sci. 66, 663–673.

    Article  PubMed  CAS  Google Scholar 

  82. Sun A.Y., Simonyi A., and Sun G.Y. (2002) The “French Paradox” and beyond: neuroprotective effects of polyphenols. Free Radical Biol. Med. 32, 314–318.

    Article  CAS  Google Scholar 

  83. Chanvitayapongs S., Draczynska-Lusiak B., and Sun A.Y. (1997) Amelioration of oxidative stress by antioxidants and resveratrol in PC12 cells. Neuroreport 8, 1499–1502.

    Article  PubMed  CAS  Google Scholar 

  84. Draczynska-Lusiak B., Doung A., and Sun A.Y. (1998) Oxidized lipoproteins may play a role in neuronal cell death in Alzheimer disease. Mol. Chem. Neuropathol. 33, 139–148.

    PubMed  CAS  Google Scholar 

  85. Draczynska-Lusiak B., Chen Y.M., and Sun A.Y. (1998) Oxidized lipoproteins activate NF-kap-paB binding activity and apoptosis in PC12 cells. Neuroreport 9, 527–532.

    Article  PubMed  CAS  Google Scholar 

  86. Sun A.Y., Chen Y.M., James-Kracke M., et al. (1997) Ethanol-induced cell death by lipid peroxidation in PC12 cells. Neurochem. Res. 22, 1187–1192.

    Article  PubMed  CAS  Google Scholar 

  87. Sun A.Y. and Sun G.Y. (2001) Ethanol and oxidative mechanisms in the brain. J. Biomed. Sci. 8, 37–43.

    Article  PubMed  CAS  Google Scholar 

  88. Sun A.Y., Ingelman-Sundberg M., Neve E., et al. (2001) Ethanol and oxidative stress. Alcohol Clin. Exp. Res. 25, 237S-243S.

    PubMed  CAS  Google Scholar 

  89. Bastianetto S., Zheng W.H., and Quirion R. (2000) Neuroprotective abilities of resveratrol and other red wine constituents against nitric oxide-related toxicity in cultured hippocampal neurons. Br. J. Pharmacol. 131, 711–720.

    Article  PubMed  CAS  Google Scholar 

  90. Jang J.H. and Surh Y.J. (2001) Protective effects of resveratrol on hydrogen peroxide-induced apoptosis in rat pheochromocytoma (PC12) cells. Mutat. Res. 496, 181–190.

    PubMed  CAS  Google Scholar 

  91. Zini R., Morin C., Bertelli A., et al. (1999) Effects of resveratrol on the rat brain respiratory chain. Drugs Exp. Clin. Res. 25, 87–97.

    PubMed  CAS  Google Scholar 

  92. Tadolini B., Juliano C., Piu L., et al. (2000) Resveratrol inhibition of lipid peroxidation. Free Radical Res. 33, 105–114.

    Article  CAS  Google Scholar 

  93. Mizutani K., Ikeda K., Kawai Y., et al. (2001) Protective effect of resveratrol on oxidative damage in male and female stroke-prone spontaneously hypertensive rats. Clin. Exp. Pharmacol. Physiol. 28, 55–59.

    Article  PubMed  CAS  Google Scholar 

  94. Win W., Cao Z., Peng X., et al. (2002) Different effects of genistein and resveratrol on oxidative DNA damage in vitro. Mutat. Res. 513, 113–120.

    PubMed  CAS  Google Scholar 

  95. Wang Q., Xu J., Rottinghaus G.E., et al. (2002) Resveratrol protects against global cerebral ischemic injury in gerbils. Brain Res. 958, 439–447.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO

    Qun Wang & Albert Y. Sun

  2. Department of Biochemistry, University of Missouri School of Medicine, Columbia, MO

    Sue Yu, Agnes Simonyi & Grace Y. Sun

Authors
  1. Qun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sue Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Agnes Simonyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Grace Y. Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Albert Y. Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Albert Y. Sun.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, Q., Yu, S., Simonyi, A. et al. Kainic acid-mediated excitotoxicity as a model for neurodegeneration. Mol Neurobiol 31, 3–16 (2005). https://doi.org/10.1385/MN:31:1-3:003

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/MN:31:1-3:003

Index Entries

Search

Navigation