Skip to main content
SpringerLink
Log in

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

  • Chapter
  • First Online:
Acute Neuronal Injury

  • 717 Accesses

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.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • 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 103:18308–18313

    Article  PubMed  CAS  Google Scholar 

  • 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 105:666–676

    Article  PubMed  Google Scholar 

  • 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 173:231–239

    Article  PubMed  CAS  Google Scholar 

  • 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) 67:13–24

    Article  CAS  Google Scholar 

  • 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) 67:25–36

    Article  CAS  Google Scholar 

  • 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 49:695–702

    PubMed  CAS  Google Scholar 

  • Bleck TP (2005) Refractory status epilepticus. Curr Opin Crit Care 1:117–120

    Article  Google Scholar 

  • Borris DJ, Bertram EH, Kaipur J (2000) Ketamine controls prolonged status epilepticus. Epilepsy Res 42:117–122

    Article  PubMed  CAS  Google Scholar 

  • Brown AW (1977) Structural abnormalities in neurones. J Clin Pathol 30(Suppl 11):155–169

    Article  Google Scholar 

  • 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 86:455–461

    Article  PubMed  CAS  Google Scholar 

  • 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 27:9278–9293

    Article  PubMed  CAS  Google Scholar 

  • 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 25:1324–1334

    Article  PubMed  CAS  Google Scholar 

  • 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 303:1010–1014

    Article  PubMed  CAS  Google Scholar 

  • Clarke PGH (1990) Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol 181:195–213

    Article  PubMed  CAS  Google Scholar 

  • 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 31:382–390

    Article  PubMed  CAS  Google Scholar 

  • Codogno P, Meijer AJ (2005) Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ 12(Suppl 2):1509–1518

    Article  PubMed  CAS  Google Scholar 

  • Colbourne F, Sutherland GR, Auer RN (1999) Electron microscopic evidence against apoptosis as the mechanism of neuronal death in global ischemia. J Neurosci 19:4200–4210

    PubMed  CAS  Google Scholar 

  • 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 739:120–131

    Article  PubMed  CAS  Google Scholar 

  • Edinger AL, Thompson CB (2004) Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol 16:663–669

    Article  PubMed  CAS  Google Scholar 

  • 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 10:285–302

    Article  PubMed  CAS  Google Scholar 

  • 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 3:206–213

    Article  PubMed  CAS  Google Scholar 

  • 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 123:204–215

    Article  PubMed  CAS  Google Scholar 

  • Fujikawa DG (1995) The neuroprotective effect of ketamine administered after status epilepticus onset. Epilepsia 36:186–195

    Article  PubMed  CAS  Google Scholar 

  • Fujikawa DG (1996) The temporal evolution of neuronal damage from pilocarpine-induced status epilepticus. Brain Res 725:11–22

    PubMed  CAS  Google Scholar 

  • Fujikawa DG (2000) Confusion between neuronal apoptosis and activation of programmed cell death mechanisms in acute necrotic insults. Trends Neurosci 23:410–411

    Article  PubMed  CAS  Google Scholar 

  • Fujikawa DG (2002) Apoptosis: ignoring morphology and focusing on biochemical mechanisms will not eliminate confusion. Trends Pharmacol Sci 23:309–310

    Article  PubMed  CAS  Google Scholar 

  • Fujikawa DG (2005) Prolonged seizures and cellular injury: understanding the connection. Epilepsia 7:S3–S11

    Google Scholar 

  • Fujikawa DG, Daniels AH, Kim JS (1994) The competitive NMDA-receptor antagonist CGP 40116 protects against status epilepticus-induced neuronal damage. Epilepsy Res 17:207–219

    Article  PubMed  CAS  Google Scholar 

  • 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 11:1605–1614

    Article  PubMed  CAS  Google Scholar 

  • 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 98:41–53

    Article  PubMed  CAS  Google Scholar 

  • Fujikawa DG, Shinmei SS, Cai B (2000b) Seizure-induced neuronal necrosis: implications for programmed cell death mechanisms. Epilepsia 41(Suppl 6):S9–S13

    Article  PubMed  Google Scholar 

  • 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 83:229–240

    Article  PubMed  CAS  Google Scholar 

  • 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 1135:206–218

    Article  PubMed  CAS  Google Scholar 

  • Griffiths T, Evans M, Meldrum BS (1983) Intracellular calcium accumulation in rat hippocampus during seizures induced by bicuculline or L-allylglycine. Neuroscience 10:385–395

    Article  PubMed  CAS  Google Scholar 

  • Griffiths T, Evans MC, Meldrum BS (1984) Status epilepticus: the reversibility of calcium loading and acute neuronal pathological changes in the rat hippocampus. Neuroscience 12:557–567

    Article  PubMed  CAS  Google Scholar 

  • 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 74:1215–1223

    Article  PubMed  CAS  Google Scholar 

  • 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 8:1169–1181

    Article  CAS  Google Scholar 

  • 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 8:568–580

    Article  PubMed  CAS  Google Scholar 

  • 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 398:195–200

    Article  PubMed  CAS  Google Scholar 

  • 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 20:1294–1300

    Article  PubMed  CAS  Google Scholar 

  • 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 283:70–74

    Article  PubMed  CAS  Google Scholar 

  • 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 287:1056–1060

    Article  PubMed  CAS  Google Scholar 

  • 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 408:461–476

    Article  PubMed  CAS  Google Scholar 

  • 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 24:1119–1132

    Article  PubMed  CAS  Google Scholar 

  • Kondratyev A, Gale K (2000) Intracerebral injection of caspase-3 inhibitor prevents neuronal apoptosis after kainic acid-evoked status epilepticus. Mol Brain Res 75:216–224

    Article  PubMed  CAS  Google Scholar 

  • 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 563:234–240

    Article  PubMed  CAS  Google Scholar 

  • Lehmann A, Hagberg H, Jacobson I, Hamberger A (1985) Effects of status epilepticus on extracellular amino acids in the hippocampus. Brain Res 359:147–151

    Article  PubMed  CAS  Google Scholar 

  • 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 91:479–489

    Article  PubMed  CAS  Google Scholar 

  • Li L, Luo X, Wang X (2001) Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412:95–99

    Article  PubMed  CAS  Google Scholar 

  • 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 1098:204–211

    Article  PubMed  CAS  Google Scholar 

  • Liu CL, Siesjö BK, Hu BR (2004) Pathogenesis of hippocampal neuronal death after hypoxia-ischemia changes during brain development. Neuroscience 127:113–123

    Article  PubMed  CAS  Google Scholar 

  • Millan MH, Chapman AG, Meldrum BS (1993) Extracellular amino acid levels in hippocampus during pilocarpine-induced seizures. Epilepsy Res 14:139–148

    Article  PubMed  CAS  Google Scholar 

  • 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 27:4844–4862

    Article  PubMed  CAS  Google Scholar 

  • Narkilahti S, Pirtillä TJ, Lukasiuk K, Tuunanen J, Pitkänen A (2003) Expression and activation of caspase 3 following status epilepticus. Eur J Neurosci 18:1486–1496

    Article  PubMed  Google Scholar 

  • 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 279:24911–24914

    Article  PubMed  CAS  Google Scholar 

  • Olney JW (1969) Brain lesions, obesity and other disturbances in mice treated with monosodium glutamate. Science 164:719–721

    Article  PubMed  CAS  Google Scholar 

  • Olney JW (1971) Glutamate-induced neuronal necrosis in the infant mouse hypothalamus. An electron microscopic study. J Neuropathol Exp Neurol 30:75–90

    Article  PubMed  CAS  Google Scholar 

  • 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 337–362

    Google Scholar 

  • Olney JW, Rhee V, Ho OL (1974) Kainic acid: a powerful neurotoxic analogue of glutamate. Brain Res 77:507–512

    Article  PubMed  CAS  Google Scholar 

  • Parrish J, Li L, Klotz K, Ledwich D, Wang X, Xue D (2001) Mitochondrial endonuclease G is important for apoptosis in C elegans. Nature 412:90–94

    Article  PubMed  CAS  Google Scholar 

  • 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 147:1575–1583

    PubMed  CAS  Google Scholar 

  • 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 10:881–888

    Article  Google Scholar 

  • 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 91:7525–7529

    Article  PubMed  CAS  Google Scholar 

  • 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 4:149–159

    Article  PubMed  CAS  Google Scholar 

  • 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 414:57–60

    Article  PubMed  CAS  Google Scholar 

  • Shintani T, Klionsky DJ (2004) Autophagy in health and disease: a double-edged sword. Science 306:990–995

    Article  PubMed  CAS  Google Scholar 

  • 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 319:21–29

    Article  PubMed  CAS  Google Scholar 

  • 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 397:441–446

    Article  PubMed  CAS  Google Scholar 

  • Syntichaki P, Xu K, Driscoll M, Tavernarakis N (2002) Specific aspartyl and calpain proteases are required for neurodegeneration in C. elegans. Nature 419:939–944

    Article  PubMed  CAS  Google Scholar 

  • Syntichaki P, Samara C, Tavernarakis N (2005) The vacuolar H+-ATPase mediates intracellular acidification required for neurodegeneration in C. elegans. Curr Biol 15:1249–1254

    Article  PubMed  CAS  Google Scholar 

  • 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 280:16175–16184

    Article  PubMed  CAS  Google Scholar 

  • Tanaka K, Graham SH, Simon RP (1996) The role of excitatory neurotransmitters in seizure-induced neuronal injury in rats. Brain Res 737:59–63

    Article  PubMed  CAS  Google Scholar 

  • Tsujimoto Y, Shimizu S (2005) Another way to die: autophagic programmed cell death. Cell Death Differ 12(Suppl 2):1528–1534

    Article  PubMed  CAS  Google Scholar 

  • Tsukada T, Watanabe M, Yamashima T (2001) Implications of CAD and DNase II in ischemic neuronal necrosis specific for the primate hippocampus. J Neurochem 79:1196–1206

    Article  PubMed  CAS  Google Scholar 

  • Wade JV, Samson FE, Nelson SR, Pazdernik TL (1987) Changes in extracellular amino acids during soman- and kainic acid-induced seizures. J Neurochem 49:645–650

    Article  PubMed  CAS  Google Scholar 

  • 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 18:1285–1289

    Article  PubMed  CAS  Google Scholar 

  • 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 76:90–96

    Article  PubMed  CAS  Google Scholar 

  • 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 28:490–505

    Article  PubMed  CAS  Google Scholar 

  • 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 106:56–69

    Article  PubMed  CAS  Google Scholar 

  • Wu Y, Dong M, Toepfer NJ, Fan Y, Xu M, Zhang J (2004) Role of endonuclease G in neuronal excitotoxicity in mice. Neurosci Lett 264:203–207

    Article  Google Scholar 

  • 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 8:1932–1944

    Article  PubMed  CAS  Google Scholar 

  • 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 10:1723–1733

    Article  PubMed  CAS  Google Scholar 

  • 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 297:259–263

    Article  PubMed  CAS  Google Scholar 

  • 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 103:18314–18319

    Article  PubMed  CAS  Google Scholar 

  • 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 seizures

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurology Department, VA Greater Los Angeles Healthcare System, North Hills, CA, USA

    Denson G. Fujikawa

  2. Department of Neurology and Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Denson G. Fujikawa

Authors
  1. Denson G. Fujikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Denson G. Fujikawa .

Editor information

Editors and Affiliations

  1. Healthcare System, VA Greater Los Angeles, Plummer St. 16111, North Hills, 91343, U.S.A.

    Denson G. Fujikawa

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Fujikawa, D.G. (2010). Activation of Caspase-Independent Programmed Pathways in Seizure-Induced Neuronal Necrosis. In: Fujikawa, D. (eds) Acute Neuronal Injury. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-73226-8_17

Download citation

Publish with us

Policies and ethics

Search

Navigation