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Activation of Caspase-Independent Programmed Pathways in Seizure-Induced Neuronal Necrosis

  • Denson G. Fujikawa
Chapter

Abstract

Our current concept of how prolonged epileptic seizures (status epilepticus, or SE) kill neurons originated in the 1970s from the pioneering work done by John Olney and associates. Olney reported in 1969 that monosodium glutamate killed neurons in the hypothalamic arcuate nucleus, a region that lacks a blood–brain barrier (Olney 1969). Subsequently, Olney and associates found that administration of glutamate (GLU), the most abundant excitatory neurotransmitter in the brain, killed hypothalamic neurons in the infant mouse (Olney 1971), and that systemic administration of a GLU analogue, kainic acid (KA) to the adult rodent resulted in SE and neuronal death (Olney et al. 1974). In 1985, Olney put forth his excitotoxic hypothesis as it applies to SE (Olney 1985). This hypothesis, which states that excessive presynaptic GLU release results in the death of postsynaptic neurons, has proved to be remarkably robust, and is applicable to a wide variety of acute neuronal insults, as mentioned in the Introduction.

Keywords

Status Epilepticus Kainic Acid Piriform Cortex Monosodium Glutamate Cellular Necrosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Andrabi SA, Kim S-W, Wang H, Koh DW, Sasaki M, Klaus JA, Otsuka T, Zhang Z, Koehler RC, Hurn PD, Poirier GG, Dawson VL, Dawson TM (2006) Poly(ADP-ribose) (PAR) polymer is a death signal. Proc Natl Acad Sci USA 103:18308–18313PubMedCrossRefGoogle Scholar
  2. Araújo IM, Gil JM, Carreira BP, Mohapel P, Petersen A, Pinheiro PS, Soulet D, Bahr BA, Brundin P, Carvalho CM (2008) Calpain activation is involved in early caspase-independent neurodegeneration in the hippocampus following status epilepticus. J Neurochem 105:666–676PubMedCrossRefGoogle Scholar
  3. Artal-Sanz M, Samara C, Syntichaki P, Tavernarakis N (2006) Lysosomal biogenesis and function is critical for necrotic cell death in Caenorhabditis elegans. J Cell Biol 173:231–239PubMedCrossRefGoogle Scholar
  4. Auer RN, Kalimo H, Olsson Y, Siesjo BK (1985a) The temporal evolution of hypoglycemic brain damage. I. Light- and electron-microscopic findings in the rat cerebral cortex. Acta Neuropathol (Berl) 67:13–24CrossRefGoogle Scholar
  5. Auer RN, Kalimo H, Olsson Y, Siesjo BK (1985b) The temporal evolution of hypoglycemic brain damage. II. Light- and electron-microscopic findings in the hippocampal gyrus and subiculum of the rat. Acta Neuropathol (Berl) 67:25–36CrossRefGoogle Scholar
  6. Bizat N, Galas MC, Jacquard C, Boyer F, Hermel JM, Schiffmann SN, Hantraye P, Blum D, Brouillet E (2005) Neuroprotective effect of zVAD against the neurotoxin 3-nitropropionic acid involves inhibition of calpain. Neuropharmacology 49:695–702PubMedGoogle Scholar
  7. Bleck TP (2005) Refractory status epilepticus. Curr Opin Crit Care 1:117–120CrossRefGoogle Scholar
  8. Borris DJ, Bertram EH, Kaipur J (2000) Ketamine controls prolonged status epilepticus. Epilepsy Res 42:117–122PubMedCrossRefGoogle Scholar
  9. Brown AW (1977) Structural abnormalities in neurones. J Clin Pathol 30(Suppl 11):155–169CrossRefGoogle Scholar
  10. Bruhn T, Cobo M, Berg M, Diemer NH (1992) Limbic seizure-induced changes in extracellular amino acid levels in the hippocampal formation: a microdialysis study of freely moving rats. Acta Neurol Scand 86:455–461PubMedCrossRefGoogle Scholar
  11. Cao G, Xing J, Xiao X, Liou AK, Gao Y, Yin XM, Clark RS, Graham SH, Chen J (2007) Critical role of calpain I in mitochondrial release of apoptosis-inducing factor in ischemic neuronal injury. J Neurosci 27:9278–9293PubMedCrossRefGoogle Scholar
  12. Cheung EC, Melanson-Drapeau L, Cregan SP, Vanderluit JL, Ferguson KL, McIntosh WC, Park DS, Bennett SA, Slack RS (2005) Apoptosis-inducing factor is a key factor in neuronal cell death propagated by BAX-dependent and BAX-independent mechanisms. J Neurosci 25:1324–1334PubMedCrossRefGoogle Scholar
  13. Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, Green DR (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303:1010–1014PubMedCrossRefGoogle Scholar
  14. Clarke PGH (1990) Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol 181:195–213PubMedCrossRefGoogle Scholar
  15. Clifford DB, Olney JW, Benz AM, Fuller TA, Zorumski CF (1990) Ketamine, phencyclidine, and MK-801 protect against kainic-acid-induced seizure-related brain damage. Epilepsia 31:382–390PubMedCrossRefGoogle Scholar
  16. Codogno P, Meijer AJ (2005) Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ 12(Suppl 2):1509–1518PubMedCrossRefGoogle Scholar
  17. Colbourne F, Sutherland GR, Auer RN (1999) Electron microscopic evidence against apoptosis as the mechanism of neuronal death in global ischemia. J Neurosci 19:4200–4210PubMedGoogle Scholar
  18. Colicos MA, Dash PK (1996) Apoptotic morphology of dentate granule cells following experimental cortical impact injury in rats: possible role in spatial memory deficits. Brain Res 739:120–131PubMedCrossRefGoogle Scholar
  19. Edinger AL, Thompson CB (2004) Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol 16:663–669PubMedCrossRefGoogle Scholar
  20. Evans MC, Griffiths T, Meldrum BS (1984) Kainic-acid seizures and the reversibility of calcium loading in vulnerable neurons in the hippocampus. Neuropathol Appl Neurobiol 10:285–302PubMedCrossRefGoogle Scholar
  21. Fariello RG, Golden GT, Smith GG, Reyes PF (1989) Potentiation of kainic acid epileptogenicity and sparing from neuronal damage by an NMDA receptor antagonist. Epilepsy Res 3:206–213PubMedCrossRefGoogle Scholar
  22. Fix AS, Horn JW, Wightman KA et al (1993) Neuronal vacuolization and necrosis induced by the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK(+)801 (dizocilpine maleate): a light and electron microscopic evaluation of the rat retrosplenial cortex. Exp Neurol 123:204–215PubMedCrossRefGoogle Scholar
  23. Fujikawa DG (1995) The neuroprotective effect of ketamine administered after status epilepticus onset. Epilepsia 36:186–195PubMedCrossRefGoogle Scholar
  24. Fujikawa DG (1996) The temporal evolution of neuronal damage from pilocarpine-induced status epilepticus. Brain Res 725:11–22PubMedGoogle Scholar
  25. Fujikawa DG (2000) Confusion between neuronal apoptosis and activation of programmed cell death mechanisms in acute necrotic insults. Trends Neurosci 23:410–411PubMedCrossRefGoogle Scholar
  26. Fujikawa DG (2002) Apoptosis: ignoring morphology and focusing on biochemical mechanisms will not eliminate confusion. Trends Pharmacol Sci 23:309–310PubMedCrossRefGoogle Scholar
  27. Fujikawa DG (2005) Prolonged seizures and cellular injury: understanding the connection. Epilepsia 7:S3–S11Google Scholar
  28. Fujikawa DG, Daniels AH, Kim JS (1994) The competitive NMDA-receptor antagonist CGP 40116 protects against status epilepticus-induced neuronal damage. Epilepsy Res 17:207–219PubMedCrossRefGoogle Scholar
  29. Fujikawa DG, Shinmei SS, Cai B (1999) Lithium-pilocarpine-induced status epilepticus produces necrotic neurons with internucleosomal DNA fragmentation in adult rats. Eur J Neurosci 11:1605–1614PubMedCrossRefGoogle Scholar
  30. Fujikawa DG, Shinmei SS, Cai B (2000a) Kainic acid-induced seizures produce necrotic, not apoptotic, neurons with internucleosomal DNA cleavage: implications for programmed cell death mechanisms. Neuroscience 98:41–53PubMedCrossRefGoogle Scholar
  31. Fujikawa DG, Shinmei SS, Cai B (2000b) Seizure-induced neuronal necrosis: implications for programmed cell death mechanisms. Epilepsia 41(Suppl 6):S9–S13PubMedCrossRefGoogle Scholar
  32. Fujikawa DG, Ke X, Trinidad RB, Shinmei SS, Wu A (2002) Caspase-3 is not activated in seizure-induced neuronal necrosis with internucleosomal DNA cleavage. J Neurochem 83:229–240PubMedCrossRefGoogle Scholar
  33. Fujikawa DG, Shinmei SS, Zhao S, Aviles ER Jr (2007) Caspase-dependent programmed cell death pathways are not activated in generalized seizure-induced neuronal death. Brain Res 1135:206–218PubMedCrossRefGoogle Scholar
  34. Griffiths T, Evans M, Meldrum BS (1983) Intracellular calcium accumulation in rat hippocampus during seizures induced by bicuculline or L-allylglycine. Neuroscience 10:385–395PubMedCrossRefGoogle Scholar
  35. Griffiths T, Evans MC, Meldrum BS (1984) Status epilepticus: the reversibility of calcium loading and acute neuronal pathological changes in the rat hippocampus. Neuroscience 12:557–567PubMedCrossRefGoogle Scholar
  36. Henshall DC, Chen J, Simon RP (2000) Involvement of caspase-3-like protease in the mechanism of cell death following focally evoked limbic seizures. J Neurochem 74:1215–1223PubMedCrossRefGoogle Scholar
  37. Henshall DC, Bonislawski DP, Skradski SL, Araki T, Lan J-Q, Schindler CK, Meller R, Simon RP (2001a) Formation of the Apaf-1/cytochrome c complex precedes activation of caspase-9 during seizure-induced neuronal death. Cell Death Diff 8:1169–1181CrossRefGoogle Scholar
  38. Henshall DC, Bonislawski DP, Skradski SL, Lan J-Q, Meller R, Simon RP (2001b) Cleavage of Bid may amplify caspase-8-induced neuronal death following focally evoked limbic seizures. Neurobiol Dis 8:568–580PubMedCrossRefGoogle Scholar
  39. Heo K, Cho Y-J, Cho K-J, Kim H-W, Kim H-J, Shin HY, Lee BI, Kim GW (2006) Minocycline inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after treatment with kainic acid in mice. Neurosci Lett 398:195–200PubMedCrossRefGoogle Scholar
  40. Hu BR, Liu CL, Ouyang Y, Blomgren K, Siejö BK (2000) Involvement of caspase-3 in cell death after hypoxia-ischemia declines during brain maturation. J Cereb Blood Flow Metab 20:1294–1300PubMedCrossRefGoogle Scholar
  41. Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler V, Dikranian K, Tenkova TI, Stefovska V, Turksi L, Olney JW (1999) Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 283:70–74PubMedCrossRefGoogle Scholar
  42. Ikonomidou C, Bittigau P, Ishimaru MJ, Wozniak DF, Koch C, Genz K, Price MT, Stefovska V, Horster F, Tenkova T, Dikranian K, Olney JW (2000) Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 287:1056–1060PubMedCrossRefGoogle Scholar
  43. Ishimaru MJ, Ikonomidou C, Tenkova TI, Der TC, Dikranian K, Sesma MA, Olney JW (1999) Distinguishing excitotoxic from apoptotic neurodegeneration in the developing rat brain. J Comp Neurol 408:461–476PubMedCrossRefGoogle Scholar
  44. Knoblach SM, Alroy DA, Nikolaeva M, Cernak I, Stoica BA, Faden AI (2004) Caspase inhibitor z-DEVD-fmk attenuates calpain and necrotic cell death in vitro and after traumatic brain injury. J Cereb Blood Flow Metab 24:1119–1132PubMedCrossRefGoogle Scholar
  45. Kondratyev A, Gale K (2000) Intracerebral injection of caspase-3 inhibitor prevents neuronal apoptosis after kainic acid-evoked status epilepticus. Mol Brain Res 75:216–224PubMedCrossRefGoogle Scholar
  46. Lallement G, Carpentier P, Collet A, Pernot-Marino I, Baubichon D, Blanchet G (1991) Effects of soman-induced seizures on different extracellular amino acid levels and on glutamate uptake in rat hippocampus. Brain Res 563:234–240PubMedCrossRefGoogle Scholar
  47. Lehmann A, Hagberg H, Jacobson I, Hamberger A (1985) Effects of status epilepticus on extracellular amino acids in the hippocampus. Brain Res 359:147–151PubMedCrossRefGoogle Scholar
  48. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479–489PubMedCrossRefGoogle Scholar
  49. Li L, Luo X, Wang X (2001) Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412:95–99PubMedCrossRefGoogle Scholar
  50. Li T, Lu C, Xia Z, Xiao B, Luo Y (2006) Inhibition of caspase-8 attenuates neuronal death induced by limbic seizures in a cytochrome c-dependent and Smac/DIABLO-independent way. Brain Res 1098:204–211PubMedCrossRefGoogle Scholar
  51. Liu CL, Siesjö BK, Hu BR (2004) Pathogenesis of hippocampal neuronal death after hypoxia-ischemia changes during brain development. Neuroscience 127:113–123PubMedCrossRefGoogle Scholar
  52. Millan MH, Chapman AG, Meldrum BS (1993) Extracellular amino acid levels in hippocampus during pilocarpine-induced seizures. Epilepsy Res 14:139–148PubMedCrossRefGoogle Scholar
  53. Moubarak RS, Yuste VJ, Artus C, Bouharrour A, Greer PA, Menissier-de Murcia J, Susin SA (2007) Sequential activation of poly(ADP-ribose) polymerase 1, calpains, and Bax is essential in apoptosis-inducing factor-mediated programmed necrosis. Mol Cell Biol 27:4844–4862PubMedCrossRefGoogle Scholar
  54. Narkilahti S, Pirtillä TJ, Lukasiuk K, Tuunanen J, Pitkänen A (2003) Expression and activation of caspase 3 following status epilepticus. Eur J Neurosci 18:1486–1496PubMedCrossRefGoogle Scholar
  55. Nur-E-Kamal A, Gross SR, Pan Z, Balklava Z, Ma J, Liu LF (2004) Nuclear translocation of cytochrome c during apoptosis. J Biol Chem 279:24911–24914PubMedCrossRefGoogle Scholar
  56. Olney JW (1969) Brain lesions, obesity and other disturbances in mice treated with monosodium glutamate. Science 164:719–721PubMedCrossRefGoogle Scholar
  57. Olney JW (1971) Glutamate-induced neuronal necrosis in the infant mouse hypothalamus. An electron microscopic study. J Neuropathol Exp Neurol 30:75–90PubMedCrossRefGoogle Scholar
  58. Olney JW (1985) Excitatory transmitters and epilepsy-related brain damage. In: Smythies JR, Bradley RJ (eds) International review of neurobiology, vol 27. Academic, Orlando, pp 337–362Google Scholar
  59. Olney JW, Rhee V, Ho OL (1974) Kainic acid: a powerful neurotoxic analogue of glutamate. Brain Res 77:507–512PubMedCrossRefGoogle Scholar
  60. Parrish J, Li L, Klotz K, Ledwich D, Wang X, Xue D (2001) Mitochondrial endonuclease G is important for apoptosis in C elegans. Nature 412:90–94PubMedCrossRefGoogle Scholar
  61. Rink A, Fung KM, Trojanowski JQ, Lee VM-Y, Neugebauer E, McIntosh TK (1995) Evidence of apoptotic cell death after experimental traumatic brain injury in the rat. Am J Pathol 147:1575–1583PubMedGoogle Scholar
  62. Rozman-Pungerčar J, Kopitar-Jerala N, Bogyo M, Turk D, Vasiljeva O, Štefe I, Vandenabeele P, Brőmme D, Pulzdar V, Fonović M, Trstenjak-Prebanda M, Dolenc I, Turk V, Turk B (2003) Inhibition of papain-like cysteine proteases and legumain by caspase-specific inhibitors: when reaction mechanism is more important than specificity. Cell Death Diff 10:881–888CrossRefGoogle Scholar
  63. Sakhi S, Bruce A, Sun N, Tocco G, Baudry M, Schreiber SS (1994) p53 induction is associated with neuronal damage in the central nervous system. Proc Natl Acad Sci USA 91:7525–7529PubMedCrossRefGoogle Scholar
  64. Schreiber SS, Tocco G, Najm I, Thompson RF, Baudry M (1993) Cycloheximide prevents kainate-induced neuronal death and c-fos expression in adult rat brain. J Mol Neurosci 4:149–159PubMedCrossRefGoogle Scholar
  65. Shacka JJ, Lu J, Xie ZL, Uchiyama Y, Roth KA, Zhang J (2007) Kainic acid induces early and transient autophagic stress in mouse hippocampus. Neurosci Lett 414:57–60PubMedCrossRefGoogle Scholar
  66. Shintani T, Klionsky DJ (2004) Autophagy in health and disease: a double-edged sword. Science 306:990–995PubMedCrossRefGoogle Scholar
  67. Smolders I, Van Belle K, Ebinger G, Michotte Y (1997) Hippocampal and cerebellar extracellular amino acids during pilocarpine-induced seizures in freely moving rats. Eur J Pharmacol 319:21–29PubMedCrossRefGoogle Scholar
  68. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397:441–446PubMedCrossRefGoogle Scholar
  69. Syntichaki P, Xu K, Driscoll M, Tavernarakis N (2002) Specific aspartyl and calpain proteases are required for neurodegeneration in C. elegans. Nature 419:939–944PubMedCrossRefGoogle Scholar
  70. Syntichaki P, Samara C, Tavernarakis N (2005) The vacuolar H+-ATPase mediates intracellular acidification required for neurodegeneration in C. elegans. Curr Biol 15:1249–1254PubMedCrossRefGoogle Scholar
  71. Takano J, Tomioka M, Tsubuki S, Higuchi M, Nobuhisa Iwata N, Itohara S, Maki M, Saido TC (2005) Calpain mediates excitotoxic DNA fragmentation via mitochondrial pathways in adult brains: evidence from calpastatin mutant mice. J Biol Chem 280:16175–16184PubMedCrossRefGoogle Scholar
  72. Tanaka K, Graham SH, Simon RP (1996) The role of excitatory neurotransmitters in seizure-induced neuronal injury in rats. Brain Res 737:59–63PubMedCrossRefGoogle Scholar
  73. Tsujimoto Y, Shimizu S (2005) Another way to die: autophagic programmed cell death. Cell Death Differ 12(Suppl 2):1528–1534PubMedCrossRefGoogle Scholar
  74. Tsukada T, Watanabe M, Yamashima T (2001) Implications of CAD and DNase II in ischemic neuronal necrosis specific for the primate hippocampus. J Neurochem 79:1196–1206PubMedCrossRefGoogle Scholar
  75. Wade JV, Samson FE, Nelson SR, Pazdernik TL (1987) Changes in extracellular amino acids during soman- and kainic acid-induced seizures. J Neurochem 49:645–650PubMedCrossRefGoogle Scholar
  76. Wang SJ, Wang SH, Song ZF, Liu XW, Wang R, Chi ZF (2007) Poly(ADP-ribose) polymerase inhibitor is neuroprotective in epileptic rat via apoptosis-inducing factor and Akt signaling. Neuroreport 18:1285–1289PubMedCrossRefGoogle Scholar
  77. Wang S, Wang S, Shan P, Song Z, Dai T, Wang R, Chi Z (2008) mu-Calpain mediates hippocampal neuron death in rats after lithium-pilocarpine-induced status epilepticus. Brain Res Bull 76:90–96PubMedCrossRefGoogle Scholar
  78. Whalen MJ, Dalkara T, You Z, Qiu J, Bermpohl D, Mehta N, Suter B, Bhide PG, Lo EH, Ericsson M, Moskowitz MA (2008) Acute plasmalemmal permeability and protracted clearance of injured cells after controlled cortical impact in mice. J Cereb Blood Flow Metab 28:490–505PubMedCrossRefGoogle Scholar
  79. Windelborn JA, Lipton P (2008) Lysosomal release of cathepsins causes ischemic damage in the rat hippocampal slice and depends on NMDA-mediated calcium influx, arachidonic acid metabolism, and free radical production. J Neurochem 106:56–69PubMedCrossRefGoogle Scholar
  80. Wu Y, Dong M, Toepfer NJ, Fan Y, Xu M, Zhang J (2004) Role of endonuclease G in neuronal excitotoxicity in mice. Neurosci Lett 264:203–207CrossRefGoogle Scholar
  81. Yamashima T, Saido TC, Takita M, Miyazawa A, Yamano J, Miyakawa A, Nishiyo H, Yamashima J, Kawashima S, Ono T, Yoshioka T (1996) Transient brain ischemia provokes Ca2+, PIP2 and calpain responses prior to delayed neuronal death in monkeys. Eur J Neurosci 8:1932–1944PubMedCrossRefGoogle Scholar
  82. Yamashima T, Kohda Y, Tsuchiya K, Ueno T, Yamashita J, Yoshioka T, Kominami E (1998) Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074: a novel strategy for neuroprotection based on ‘calpain-cathepsin hypothesis’. Eur J Neurosci 10:1723–1733PubMedCrossRefGoogle Scholar
  83. Yu S-W, Wang H, Poitras MF, Coombs C, Bowers WJ, Federoff HJ, Poirier GG, Dawson TM, Dawson VL (2002) Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 297:259–263PubMedCrossRefGoogle Scholar
  84. Yu S-W, Andrabi SA, Wang H, Kim NS, Poirier GG, Dawson TM, Dawson VL (2006) Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death. Proc Natl Acad Sci USA 103:18314–18319PubMedCrossRefGoogle Scholar
  85. Zhao S, Aviles ER Jr, Fujikawa DG (Submitted for publication) Nuclear translocation of mitochondrial cytochrome c and lysosomal cathepsins B and D within the first 60 minutes of generalized seizuresGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Neurology DepartmentVA Greater Los Angeles Healthcare SystemNorth HillsUSA
  2. 2.Department of Neurology and Brain Research InstituteDavid Geffen School of Medicine, University of CaliforniaLos AngelesUSA

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