Abstract
In experimental models of epilepsy, single and recurrent seizures are often used in an attempt to determine the effects of the seizures themselves on mammalian brain function. These models attempt to emulate as many features as possible of their human disease counterparts without many of the confounding factors such as underlying disease processes and medication effects. Numerous models have been used in the past to address different questions. Nevertheless, the basic questions are often the same:
-
1.
Do seizures cause long-term damage?
-
2.
Do seizures predispose to chronic epilepsy (epileptogenesis), that is long-term spontaneous repetitive seizures?
-
3.
Are these results developmentally regulated?
-
4.
Are the underlying mechanisms of epileptogenesis and brain damage related?
In prusuing these questions, the goal is to detemine how seizures exert their effecets and to minimize any side effects from the methods employed to induce the seizures themselves. This requires a detailed characterization of the methods used to induce seizures.
In thes chapter, we will review the literature regarding the tetanus toxin model of chronic epilepsy with regard to its mechanisms of action, clinical comparisons, how it is experimentally implemented and the results obtained thus far. These results will be compared to other models of chronic epilepsy in order to make generalizations about the effects of repetitive seizures in adult and early life. At this time, it apperas that repetitive seizures cause long-term changes in learning ability and may cause a predisposition to chronic seizures at all ages. In younger animals, both features of learning impairment and epilepsy are not typically associated with cell loss as they are in adult animals. At all ages, some form of syaptic reorganization has been demonstrated to occur.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Tetanus. In: Pickering LK, ed. Red Book: Report of the Committee on Infectious Diseases. Elk Grove: American Academy of Pediatrics, 2000: 563–568.
Volpe JJ. Bacterial and fungal intracranial infections. In: Neurology of the Newborn. Philadelphia: W.B. Saunders, 2001: 774–810.
Anaerobic infections. In Johnson KB, Oski FA, eds. Oski’s Essential Pediatrics. Philadelphia: Lippincott-Raven, 1997: 209–212.
Rossetto O, Seveso M, Caccin P et al. Tetanus and botulinum neurotoxins: turning bad guys into good by research. Toxicon 2001; 39: 27–41.
Holme-Zell B, Ecker A, Weller U et al. Synaptobrevin cleavage by the tetanus toxin light chain is linked to the inhibition of exocytosis in chromaffin cells. FEBS Letters 1994; 355: 131–134.
Schiavo G, Benfenati F, Poulain B et al. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 1992; 359: 832–834.
Herreros J, Miralles FX, Solsona C et al. Tetanus toxin inhibits spontaneous quantal release and cleaves VAMP/synaptobrevin. Brain Res 1995; 699: 165–170.
Rothman JE. Mechanisms of intracellular protein transport. Nature 1994; 372: 55–63.
Bergey GK, MacDonald RL, Habig WH et al. Tetanus toxin: convulsant action on mouse spinal neurons in culture. J Neurosci 1983; 3: 2310–2323.
Collingridge GL, Davies J. The in vitro inhibition of GABA release by tetanus toxin. Neuropharmacol 1982; 21: 851–855.
Mellanby J. Tetanus toxin as a tool for investigating the consequences of excessive neuronal excitation. In: DasGupta BR, ed. Botulinum and Tetanus Neurotoxins. New York: Plenum, 1993: 291–297.
McMahon HT, Foran P, Dolly JO et al. Tetanus toxin and botulinum toxins type A and B inhibit glutamate, gamma-aminobutyric acid, aspartate, and met-enkephalin release from synaptosomes. Clues to the locus of action. J Biol Chem 1992; 267: 21338–21343.
Curtis DR, de Groat WC. Tetanus toxin and spinal inhibition. Brain Res 1968; 10: 208–212.
Curtis DR, Felix D, Game CJA et al. Tetanus toxin and the synaptic release of GABA. Brain Res 1973; 51: 358–362.
Mellanby J, George G, Robinson A et al. Epileptiform syndrome in rats produced by injecting tetanus toxin into the hippocampus. J Neurol Neurosurg Psychiatry 1977; 40: 404–414.
Matteoli M, Verderio C, Rossetto O et al. Synaptic vesicle endocytosis mediates the entry of tetanus neurotoxin into hippocampal neurons. Proc Natl Acad Sci USA 1996; 93: 13310–13315.
Lledo PM, Zhang X, Sudhof TC et al. Postsynaptic membrane fusion and long-term potentiation. Science 1998; 279: 399–403.
Lin JW, Sheng M. NSF and AMPA receptors get physical. Neuron 1998; 21: 267–270.
Ouardouz M, Sastry BR. Mechanisms underlying LTP of inhibitory synaptic transmission in the deep cerebellar nuclei. J Neurophysiol 2000; 84: 1414–1421.
Lu W-Y, Man H-Y, Ju W et al. Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons. Neuron 2001; 29: 243–254.
Whittington MA, Jefferys JGR. Epileptic activity outlasts disinhibition after intrahippocampal tetanus toxin in the rat. J Physiol 1994; 481: 593–604.
Fishman PS, Savitt JM. Transsynaptic transfer of retrogradely transported tetanus protein-peroxidase conjugates. Exp Neurol 1989; 106: 197–203.
Schwab ME, Suka K, Thoenen H. Selective retrograde transsynaptic transfer of a protein, tetanus toxin, subsequent to its retrograde axonal transport. J Cell Biol 1979; 82: 798–810.
Amaral DG, Witter MP. The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 1989; 31: 571–591.
Lee CL, Hannay J, Hrachovy R et al. Spatial learning deficits without hippocampal neuronal loss in a model of early-onset epilepsy. Neuroscience 2001; 107: 71–84.
Lee CL, Hrachovy RA, Smith KL et al. Tetanus toxin-induced seizures in infant rats and their effects on hippocampal excitability in adulthood. Brain Res 1995; 677: 97–109.
Brener K, Amitai Y, Jefferys JGR et al Chronic epileptic foci in neocortex: In vivo and in vitro effects of tetanus toxin. Eur J Neurosci 1991; 3: 47–54.
Darcey TM, Williamson PD. Chronic/semichronic limbic epilepsy produced by microinjection of tetanus toxin in cat hippocampus. Epilepsia 1992; 33: 402–419.
Duchen LW, Tonge DA. The effects of tetanus toxin on neuromuscular transmission and on the morphology of motor end-plates in slow and fast skeletal muscle of the mouse. J Physiol 1973; 228: 157–172.
Critchley DR, Nelson PG, Habig WH et al. Fate of tetanus toxin bound to the surface of primary neurons in culture: evidence for rapid internalization. J Cell Biol 1985; 100: 1499–1507.
Erdal E, Bartels F, Binscheck T et al. Processing of tetanus and botulinum A neurotoxin in isolated chromaffin cells. Naunyn Schmiedebergs Arch Pharmacol 1995; 351: 67–78.
Habig WH, Bigalke H, Bergey GK et al. Tetanus toxin in dissociated spinal cord cultures: long-term characterization of form and action. J Neurochem 1986; 47: 930–937.
Mellanby JH. Elimination of 125I from rat brain after injection of small doses of 125I-labelled tetanus toxin into the hippocampus. Neurosci Lett Suppl 1989; Suppl 36: S55
Empson RM, Jefferys JGR. Synaptic inhibition in primary and secondary chronic epileptic foci induced by intrahippocampal tetanus toxin in the rat. J Physiol 1993; 465: 595–614.
Roux E, Borrel A. Tetanos cerebral et immunite contre le tetanos. Ann Inst Pasteur 1898; 4: 225–239.
Louis ED, Williamson PD, Darcey TM. Chronic focal epilepsy induced by microinjection of tetanus toxin into the cat motor cortex. Electroencephalogy Clin Neurophysiol 1990; 75: 548–557.
Mellanby J, Hawkins C, Mellanby H et al. Tetanus toxin as a tool for studying epilepsy. J Physiol (Paris) 1984; 79: 207–215.
Jefferys JGR, Whittington MA. Review of the role of inhibitory neurons in chronic epileptic foci induced by intracerebral tetanus toxin. Epilepsy Res 1996; 26: 59–66.
Sundstrom LE, Mellanby JH. Tetanus toxin blocks inhibition of granule cells in the dentate gyrus of the urethane-anaesthetized rat. Neuroscience 1990; 38: 621–627.
Calabresi P, Beneditti M, Mercuri NB et al. Selective depression of synaptic transmission by tetanus toxin: a comparative study on hippocampal and neostriatal slices. Neuroscience 1989; 30: 663–670.
Mellanby J, Strawbridge P, Collingridge GL et al. Behavioural correlates of an experimental hippocampal epileptiform syndrome in rats. J Neurol Neurosurg Psychiatry 1981; 44: 1084–1093.
Brace HM, Jefferys JGR, Mellanby J. Long-term changes in hippocampal physiology and learning ability of rats after intrahippocampal tetanus toxin. J Physiol (Lond) 1985; 368: 343–357.
Jefferys JGR. Chronic epileptic foci in vitro in hippocampal slices from rats with tetanus toxin epileptic syndrome. J Neurophysiol 1989; 62: 458–468.
Bliss T, Collingridge G. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 1993; 361: 31–39.
Jefferys JGR, Empson RM. Development of chronic secondary epileptic foci following intrahippocampal injection of tetanus toxin in the rat. Exp Physiol 1990; 75: 733–736.
Jordan SJ, Jefferys JGR. Sustained and selective block of IPSPs in brain slices from rats made epileptic by intrahippocampal tetanus toxin. Epilepsy Res 1992; 11: 119–129.
Shaw JAG, Perry VH, Mellanby J. Tetanus toxin-induced seizures cause microglial activation in rat hippocampus. Neurosci Lett 1990; 120: 66–69.
Bagetta G, Nistico G, Bowery NG. Prevention by the NMDA receptor antagonist, MK801 of neuronal loss produced by tetanus toxin in the rat hippocampus. Br J Pharmac 1990; 101: 776–780.
Hughes JT, Mellanby J. Experimental epilepsy induced by tetanus toxin injected into the rat hippocampus: a Golgi study. Neuropath Appl Neurobiol 1985; 11: 73
Coiling SB, Man WD-C, Draguhn A et al. Dendritic shrinkage and dye-coupling between rat hippocampal CAl pyramidal cells in the tetanus toxin model of epilepsy. Brain Res 1996; 741: 38–43.
Mitchell J, Gatherer M, Sundstrom LE. Aberrant Timm-stained fibres in the dentate gyrus following tetanus toxin-induced seizures in the rat. Neuropath Appl Neurobiol 1996; 22: 129–135.
Rosa MLNM, Jefferys JGR, Sanders MW et al. Expression of mRNAs encoding flip isoforms of G1uR1 and GluR2 glutamate receptors is increased in rat hippocampus in epilepsy induced by tetanus toxin. Epilepsy Res 2002; 36: 243–251.
Najlerahim A, Williams SF, Pearson RCA et al. Increased expression of GAD mRNA during the chronic epileptic syndrome due to intrahippocampal tetanus toxin Exp Brain Res 1992; 90: 332–342.
Mitchell J, Gatherer M, Sundstrom LE. Loss of hilar somatostatin neurons following tetanus toxin-induced seizures. Acta Neuropathologica 1995; 89: 425–430.
Mellanby J, Milward AJ. Do fits really beget fits? The effect of previous epileptic activity on the subsequent induction of the tetanus toxin model of limbic epilepsy in the rat. Neurobiol Dis 2001; 8: 679–691.
Empson RM, Amitai Y, Jefferys JGR et al. Injection of tetanus toxin into the neocortex elicits persistent epileptiform activity but only transient impairment of GABA release. Neuroscience 1993; 57: 235–239.
Liang F, Jones EG. Differential and time-dependent changes in gene expression for type II calcium/calmodulin-dependent protein kinase, 67 kDa glutamic acid decarboxylase, and glutamate receptor subunits in tetanus toxin-induced focal epilepsy. J Neurosci 1997; 17: 2168–2180.
Liang F, Jones EG. Reciprocal up-and down-regulation of BDNF mRNA in tetanus toxin-induced epileptic focus and inhibitory surround in cerebral cortex. Cerebral Cortex 1998; 8: 481–491.
Bear MF, Rittenhouse CD. Molecular basis for induction of ocular dominance plasticity. J Neurobiol 1999; 41: 83–91.
Anderson AE, Hrachovy RA, Antalffy BA et al. A chronic focal epilepsy with mossy fiber sprouting follows recurrent seizures induced by intrahippocampal tetanus toxin injection in infant rats. Neuroscience 1999; 92: 73–82.
Smith KL, Lee CL, Swann JW. Local circuit abnormalities in chronically epileptic rats after intrahippocampal tetanus toxin injection in infancy. J Neurophysiol 1998; 79: 106–116.
Jiang M, Lee CL, Smith KL et al. Spine loss and other persistent alterations of hippocampal pyramidal cell dendrites in a model of early-onset epilepsy. J Neurosci 1998; 18: 8356–8368.
Rashid S, Lee I-G, Anderson AE et al. Insights into the tetanus toxin model of early-onset epilepsy from long-term video monitoring during anticonvulsant therapy. Brain Res 1999; 118: 221–225.
Milward AJ, Meldrum BS, Mellanby JH. Forebrain ischaemia with CAl cell loss impairs epileptogenesis in the tetanus toxin limbic seizure model. Brain 1999; 122: 1009–1016.
Stafstrom CE, Thompson JL, Holmes GL. Kainic acid seizures in the developing brain: status epilepticus and spontaneous recurrent seizures. Brain Res Dev Brain Res 1992; 21: 227–236.
Esclapez M, Hirsch JC, Ben-Ari Y et al. Newly formed excitatory pathways provide a substrate for hyperexcitability in experimental temporal lobe epilepsy. J Comp Neurol 1999; 498: 449–460.
Yang Y, Tandon P, Liu Z et al. Synaptic reorganization following kainic acid-induced seizures during development. Dev Brain Res 1998; 107: 169–177.
Sarkisian MR, Tandon P, Liu Z et al. Multiple kainic acid seizures in the immature and adult brain: ictal manifestations and long-term effects on learning and memory. Epilepsia 1997; 38: 1157–1166.
Lynch M, Sayin U, Bownds J et al. Long-term consequences of early postnatal seizures on hippocampal learning and plasticity. Eur J Neurosci 2000; 12: 2252–2264.
Koh S, Storey TW, Santos TC et al. Early-life seizures in rats increase susceptibility to seizure-induced brain injury in adulthood. Neurology 1999; 53: 915–921.
Sankar R, Shin DH, Liu H et al. Patterns of status epilepticus-induced neuronal injury during development and long-term consequences. J Neurosci 1998; 18: 8382–8393.
Sankar R, Shin D, Mazarati AM et al. Epileptogenesis after status epilepticus reflects age-and model-dependent plasticity. Ann Neurol 2000; 48: 580–589.
Dube C, Marescaux C, Nehlig A. A metabolic and neuropathological approach to the understanding of plastic changes that occur in the immature and adult rat brain during lithiumpilocarpine-induced epileptogenesis. Epilepsia 2000; 41: 36–43.
Priel MR, dos Santos NF, Cavalheiro EA. Developmental aspects of the pilocarpine model of epilepsy. Epilepsy Res 1996; 26: 115–121.
dos Santos NF, Arida RM, Filho EM et al. Epileptogenesis in immature rats following recurrent status epilepticus. Brain Res Rev 2000; 32: 269–276.
Santos NF, Marques RH, Correia L et al. Multiple pilocarpine-induced status epilepticus in developing rats: a long-term behavioral and electrophysiological study. Epilepsia 2000; 41: 557–563.
Rice AC, Floyd CL, Lyeth BG et al. Status epilepticus causes long-term NMDA receptor-dependent behavioral changes and cognitive deficits. Epilepsia 1998; 39: 1148–1157.
Holmes GL, Gairsa J-L, Chevassus-Au-Louis N et al. Consequences of neonatal seizures in the rat: morphological and behavioral effects. Ann Neurol 1998; 44: 845–857.
Huang L, Cilio MR, Silveira DC et al. Long-term effects of neonatal seizures: a behavioral, electrophysiological and histological study. Brain Res Dev Brain Res 1999; 118: 99–107.
Chen K, Baram TZ, Soltesz I. Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits. Nat Med 1999; 5: 888–894.
Dube C, Chen K, Eghbal-Ahmadi M et al. Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long term. Ann Neurol 2000; 47: 336–344.
Chan K, Aradi I, Thon N et al. Persistently modified h-channels after complex febrile seizures convert the seizure-induced enhancement of inhibition to hyperexcitability. Nat Med 2001; 7: 331–337.
Sanchez RM, Koh S, Rio C et al. Decreased glutamate receptor 2 expression and enhanced epileptogenesis in immature rat hippocampus after perinatal hypoxia-induced seizures. J Neurosci 2001; 21: 8154–8163.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Springer Science+Business Media New York
About this chapter
Cite this chapter
Benke, T.A., Swann, J. (2004). The Tetanus Toxin Model of Chronic Epilepsy. In: Binder, D.K., Scharfman, H.E. (eds) Recent Advances in Epilepsy Research. Advances in Experimental Medicine and Biology, vol 548. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-6376-8_16
Download citation
DOI: https://doi.org/10.1007/978-1-4757-6376-8_16
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4419-3418-5
Online ISBN: 978-1-4757-6376-8
eBook Packages: Springer Book Archive