Publikationsserver der Universitätsbibliothek Marburg

Titel:Auswirkung der Durchtrennung des medialen Tractus perforans auf die Epileptogenese im Tractus-perforans-Stimulations-Modell der Temporallappenepilepsie
Autor:Meyer, Martin
Weitere Beteiligte: Rosenow, Felix (Prof. Dr. med)
Veröffentlicht:2017
URI:https://archiv.ub.uni-marburg.de/diss/z2017/0284
URN: urn:nbn:de:hebis:04-z2017-02846
DOI: https://doi.org/10.17192/z2017.0284
DDC: Medizin, Gesundheit
Titel(trans.):Effect of tractus perforans dissections on epileptogenesis in the tractus-perforans-stimulation animal model of temporal lobe epilepsie.
Publikationsdatum:2017-04-17
Lizenz:https://creativecommons.org/licenses/by-nc-sa/4.0

Dokument

Schlagwörter:
Dissektion, Elektroencephalographie, Ratte, Status epilepticus ,, epilepsy, hippocampus, Epilepsie, interiktale Potentiale, Hippocampus, Tiermodell, Tractus perforans, entorhinaler Kortex, tractus perforans, animal model, Entstehung, dissection, Temporallappen, Hippocampussclerose, Epileptogenese, Stimulation

Zusammenfassung:
Fragestellung: Im nicht-konvulsiven-Tractus-perforans-Stimulations (NKTPS)-Tiermodell kann über einen Zeitraum von 3 Wochen nach der 8h langen Stimulation der Hauptefferenz zum Hippocampus, des Tractus perforans (TP), eine „Latenzzeit“ ohne das Auftreten spontaner epileptischer Anfälle beobachtet werden. Während der „Latenzzeit“ wurden, durch die kontinuierliche Ableitung der elektrischen Körner-zellaktivität, spontane paroxysmal auftretende Potentiale erfasst. Diese entsprachen den durch eine niederfrequente Tractus-perforans-Stimulation evozierten Körnerzell-potentialen. Diese Beobachtung führt zu der Hypothese, dass während der Latenzzeit im entorhinalen Cortex (EC) entstehende Entladungen zu einem „kindling“ des Hip-pocampus führen, was eventuell in der Induktion einer Epilepsie gipfelt. Diese Hypo-these wurde überprüft, indem eine bilaterale TP-Transsektion unmittelbar nach der Epilepsie induzierenden Tractus-perforans-Stimulation durchgeführt wurde. Hier-durch wurde die Hauptefferenz vom EC zum Hippocampus unterbunden. Methode: Männliche Sprague-Dawly-Ratten erhielten eine bilaterale TPS über 8h, was die Entstehung einer Temporallappenepilepsie und eine klassische Hippocam-pussklerose induziert. Unmittelbar nach der TPS wurde der Tractus perforans beidsei-tig mit einem Mikromesser durchtrennt. Anschließend wurden in der Körnerzell-schicht liegende Tiefenelektroden reimplantiert. Die kontinuierliche Video-EEG Be-obachtung der Versuchstiere wurde 2 Wochen nach der letzten Stimulation begon-nen. Die chronischen neuropathologischen Veränderungen wurden histologisch frü-hestens 70 Tage nach der TPS analysiert. Die Kontrolltiere wurden identisch behan-delt, erhielten aber nur eine scheinbare Durchtrennung des TP (Trepanation der Schä-deldecke, kein Einsatz des Mikromessers, Implantation der Tiefenelektroden). Ergebnisse: Die beidseitige Durchtrennung des Tractus perforans hatte weder mess-bare Auswirkungen auf die Epileptogenese, noch auf die hippocampale Neuropatho-logie. Schlussfolgerung: Diese Daten belegen, dass die Unterbindung des Hauptzustroms vom entorhinalen Cortex zum Hippocampus keine effektive antiepileptogene Thera-pie ist. Außerdem wird die Hypothese, dass der entorhinale Cortex eine epileptogene Zone ist, die den Hippocampus während der Latenzzeit „kindled“, nicht gestützt.

Summary:
Purpose: Following stimulation of the main input to the hippocampus, the perforant pathway, in awake rats for 8 h, a seizure-free “latent period” is observed that lasts around three weeks. Continuous recording during the latent period from the dentate gyrus revealed spontaneous events that resembled low-frequency perforant pathway stimulation (PPS). This led us to hypothesize that, during the latent period, input from the entorhinal cortex kindles the hippocampus, eventually culminating in epilep-sy. We sought to test this hypothesis by removing entorhinal cortex input to the hip-pocampus immediately after pro-epileptogenic PPS. Method: Male Sprague-Dawley rats received bilateral PPS lasting 8 h, which induces temporal lobe epilepsy and classic hippocampal sclerosis. Immediately after PPS, bi-lateral mechanical transection of the performant pathway was performed with a mi-croknife. Recording electrodes were re-implanted in the dentate gyrus and animals were continuously video-EEG monitored for spontaneous seizures, beginning two weeks after PPS. Longterm neuropathology was examined histologically starting sev-enty days after PPS. Controls were treated identically, but received sham surgery (skull trephination, no microknife insertion, recording electrode reimplantation, video-EEG monitoring). Results: Bilateral angular bundle transection did not alter either epileptogenesis, e.g. the latency to epilepsy, or hippocampal neuropathology. Conclusion: These data demonstrate that removing entorhinal cortex input to the hippocampus is not an effective antiepileptogenic treatment. Furthermore, this does not support the hypothesis that the entorhinal cortex is an epileptogenic zone that kindles the hippocampus during the latent period.

Bibliographie / References

  1. Dichter, Marc A. (2009): Emerging concepts in the pathogenesis of epilepsy and epileptogenesis. In: Arch Neurol 66 (4), S. 443-447. DOI: 10.1001/archneurol.2009.10.
  2. Jobst, Barbara C.; Cascino, Gregory D. (2015): Resective epilepsy surgery for drug-resistant focal epilepsy: a review. In: JAMA 313 (3), S. 285-293. DOI: 10.1001/jama.2014.17426.
  3. Chauviere, Laetitia; Doublet, Thomas; Ghestem, Antoine; Siyoucef, Safia S.; Wendling, Fabrice; Huys, Raoul et al. (2012): Changes in interictal spike features precede the onset of temporal lobe epilepsy. In: Annals of neurology 71 (6), S. 805-814. DOI: 10.1002/ana.23549.
  4. van Paesschen, W.; Connelly, A.; King, M. D.; Jackson, G. D.; Duncan, J. S. (1997): The spectrum of hippocampal sclerosis: a quantitative magnetic resonance imaging study. In: Annals of neurology 41 (1), S. 41-51. DOI: 10.1002/ana.410410109.
  5. Bumanglag, Argyle V.; Sloviter, Robert S. (2008): Minimal latency to hippocampal epileptogenesis and clinical epilepsy after perforant pathway stimulation-induced status epilepticus in awake rats. In: The Journal of comparative neurology 510 (6), S. 561-580. DOI: 10.1002/cne.21801.
  6. Lewis, Frederic T. (1923): The significance of the termHippocampus. In: J. Comp. Neurol. 35 (3), S. 213-230. DOI: 10.1002/cne.900350303.
  7. Cortical afferents. In: The Journal of comparative neurology 264 (3), S. 356-395. DOI: 10.1002/cne.902640306.
  8. Ishizuka, N.; Weber, J.; Amaral, D. G. (1990): Organization of intrahippocampal projections originating from CA3 pyramidal cells in the rat. In: The Journal of comparative neurology 295 (4), S. 580-623. DOI: 10.1002/cne.902950407.
  9. Del Turco, Domenico; Woods, Alisa G.; Gebhardt, Carl; Phinney, Amie L.; Jucker, Mathias; Frotscher, Michael; Deller, Thomas (2003): Comparison of commissural sprouting in the mouse and rat fascia dentata after entorhinal cortex lesion. In: Hippocampus 13 (6), S. 685- 699. DOI: 10.1002/hipo.10118.
  10. Kelley, M. S.; Steward, O. (1996): The process of reinnervation in the dentate gyrus of adult rats: physiological events at the time of the lesion and during the early postlesion period. In: Experimental neurology 139 (1), S. 73-82. DOI: 10.1006/exnr.1996.0082.
  11. Lerche, H.; Vezzani, A.; Beck, H.; Blümcke, I.; Weber, Y.; Elger, C. (2011): Neue Entwicklungen der Epileptogenese und therapeutische Perspektiven. In: Nervenarzt 82 (8), S. 978- 985. DOI: 10.1007/s00115-011-3260-4.
  12. Levesque, Maxime; Avoli, Massimo; Bernard, Christophe (2015): Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration. In: Journal of neuroscience methods. DOI: 10.1016/j.jneumeth.2015.03.009.
  13. Gorter, Jan A.; van Vliet, Erwin A.; Lopes da Silva, Fernando H (2015b): Which insights have we gained from the kindling and post-status epilepticus models? In: Journal of neuroscience methods. DOI: 10.1016/j.jneumeth.2015.03.025.
  14. Boison, Detlev (2015): Adenosinergic signaling in epilepsy. In: Neuropharmacology. DOI: 10.1016/j.neuropharm.2015.08.046.
  15. Gorter, Jan A.; van Vliet, Erwin A.; Aronica, Eleonora (2015a): Status epilepticus, bloodbrain barrier disruption, inflammation, and epileptogenesis. In: Epilepsy & behavior : E&B 49, S. 13-16. DOI: 10.1016/j.yebeh.2015.04.047.
  16. Bernhardt, Boris C.; Bonilha, Leonardo; Gross, Donald W. (2015): Network analysis for a network disorder: The emerging role of graph theory in the study of epilepsy. In: Epilepsy & behavior : E&B. DOI: 10.1016/j.yebeh.2015.06.005.
  17. Newton, Charles R.; Garcia, Hector H. (2012): Epilepsy in poor regions of the world. In: Lancet (London, England) 380 (9848), S. 1193-1201. DOI: 10.1016/S0140-6736(12)61381-6.
  18. Deisseroth, Karl (2011): Optogenetics. In: Nature methods 8 (1), S. 26-29. DOI: 10.1038/nmeth.f.324.
  19. Boyden, Edward S.; Zhang, Feng; Bamberg, Ernst; Nagel, Georg; Deisseroth, Karl (2005): Millisecond-timescale, genetically targeted optical control of neural activity. In: Nature neuroscience 8 (9), S. 1263-1268. DOI: 10.1038/nn1525.
  20. van Strien, N. M.; Cappaert, N. L. M.; Witter, M. P. (2009): The anatomy of memory: an interactive overview of the parahippocampal-hippocampal network. In: Nature reviews. Neuroscience 10 (4), S. 272-282. DOI: 10.1038/nrn2614.
  21. Moser, Edvard I.; Roudi, Yasser; Witter, Menno P.; Kentros, Clifford; Bonhoeffer, Tobias; Moser, May-Britt (2014): Grid cells and cortical representation. In: Nat Rev Neurosci 15 (7), S. 466-481. DOI: 10.1038/nrn3766.
  22. Meyer, Martin; Kienzler-Norwood, Friederike; Bauer, Sebastian; Rosenow, Felix; Norwood, Braxton A. (2016): Removing entorhinal cortex input to the dentate gyrus does not impede low frequency oscillations, an EEG-biomarker of hippocampal epileptogenesis. In: Scientific reports 6, S. 25660. DOI: 10.1038/srep25660.
  23. Blumcke, Ingmar; Thom, Maria; Aronica, Eleonora; Armstrong, Dawna D.; Bartolomei, Fabrice; Bernasconi, Andrea et al. (2013): International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a Task Force report from the ILAE Commission on Diagnostic Methods. In: Epilepsia 54 (7), S. 1315-1329. DOI: 10.1111/epi.12220.
  24. Haneef, Zulfi; Lenartowicz, Agatha; Yeh, Hsiang J.; Levin, Harvey S.; Engel, Jerome, JR; Stern, John M. (2014): Functional connectivity of hippocampal networks in temporal lobe epilepsy. In: Epilepsia 55 (1), S. 137-145. DOI: 10.1111/epi.12476.
  25. Jin, Seung-Hyun; Jeong, Woorim; Chung, Chun Kee (2015): Mesial temporal lobe epilepsy with hippocampal sclerosis is a network disorder with altered cortical hubs. In: Epilepsia 56 (5), S. 772-779. DOI: 10.1111/epi.12966.
  26. Bragin, Anatol; Wilson, Charles L.; Almajano, Joyel; Mody, Istvan; Engel, Jerome, JR (2004): High-frequency oscillations after status epilepticus: epileptogenesis and seizure genesis. In: Epilepsia 45 (9), S. 1017-1023. DOI: 10.1111/j.0013-9580.2004.17004.x.
  27. Fisher, Robert S.; van Emde Boas, Walter; Blume, Warren; Elger, Christian; Genton, Pierre; Lee, Phillip; Engel, Jerome, JR (2005): Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). In: Epilepsia 46 (4), S. 470-472. DOI: 10.1111/j.0013-9580.2005.66104.x.
  28. Preusser, M.; Laggner, U.; Haberler, C.; Heinzl, H.; Budka, H.; Hainfellner, J. A. (2006): Comparative analysis of NeuN immunoreactivity in primary brain tumours: conclusions for rational use in diagnostic histopathology. In: Histopathology 48 (4), S. 438-444. DOI: 10.1111/j.1365-2559.2006.02359.x.
  29. Blumenfeld, Hal; Lampert, Angelika; Klein, Joshua P.; Mission, John; Chen, Michael C.; Rivera, Maritza et al. (2009): Role of hippocampal sodium channel Nav1.6 in kindling epileptogenesis. In: Epilepsia 50 (1), S. 44-55. DOI: 10.1111/j.1528-1167.2008.01710.x.
  30. Ngugi, Anthony K.; Bottomley, Christian; Kleinschmidt, Immo; Sander, Josemir W.; Newton, Charles R. (2010): Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. In: Epilepsia 51 (5), S. 883-890. DOI: 10.1111/j.1528-1167.2009.02481.x.
  31. Lerche, Holger; Shah, Mala; Beck, Heinz; Noebels, Jeff; Johnston, Dan; Vincent, Angela (2013): Ion channels in genetic and acquired forms of epilepsy. In: The Journal of physiology 591 (Pt 4), S. 753-764. DOI: 10.1113/jphysiol.2012.240606.
  32. Löscher, Wolfgang; Brandt, Claudia (2010): Prevention or modification of epileptogenesis after brain insults: experimental approaches and translational research. In: Pharmacol. Rev. 62 (4), S. 668-700. DOI: 10.1124/pr.110.003046.
  33. Giblin, Kathryn A.; Blumenfeld, Hal (2010): Is epilepsy a preventable disorder? New evidence from animal models. In: Neuroscientist 16 (3), S. 253-275. DOI: 10.1177/1073858409354385.
  34. Nevalainen, Olli; Ansakorpi, Hanna; Simola, Mikko; Raitanen, Jani; Isojarvi, Jouko; Artama, Miia; Auvinen, Anssi (2014): Epilepsy-related clinical characteristics and mortality: a systematic review and meta-analysis. In: Neurology 83 (21), S. 1968-1977. DOI: 10.1212/WNL.0000000000001005.
  35. Golub, Victoria M.; Brewer, Jonathan; Wu, Xin; Kuruba, Ramkumar; Short, Jenessa; Manchi, Maunica et al. (2015): Neurostereology protocol for unbiased quantification of neuronal injury and neurodegeneration. In: Frontiers in aging neuroscience 7, S. 196. DOI: 10.3389/fnagi.2015.00196.
  36. Miller, Daniel J.; Balaram, Pooja; Young, Nicole A.; Kaas, Jon H. (2014): Three counting methods agree on cell and neuron number in chimpanzee primary visual cortex. In: Frontiers in neuroanatomy 8, S. 36. DOI: 10.3389/fnana.2014.00036.
  37. Jinde, Seiichiro; Zsiros, Veronika; Nakazawa, Kazu (2013): Hilar mossy cell circuitry controlling dentate granule cell excitability. In: Frontiers in neural circuits 7, S. 14. DOI: 10.3389/fncir.2013.00014.
  38. Chung, Sungkwon; Spruston, Nelson; Koh, Sookyong (2015): Age-dependent changes in intrinsic neuronal excitability in subiculum after status epilepticus. In: PloS one 10 (3), S.
  39. Bragin, Anatol; Azizyan, Avetis; Almajano, Joyel; Wilson, Charles L.; Engel, Jerome, JR (2005): Analysis of chronic seizure onsets after intrahippocampal kainic acid injection in freely moving rats. In: Epilepsia 46 (10), S. 1592-1598. DOI: 10.1111/j.1528- 1167.2005.00268.x.
  40. Matthews, D. A.; Cotman, C.; Lynch, G. (1976): An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. I. Magnitude and time course of degeneration. In: Brain research 115 (1), S. 1-21.
  41. Blumcke, Ingmar; Pauli, Elisabeth; Clusmann, Hans; Schramm, Johannes; Becker, Albert; Elger, Christian et al. (2007): A new clinico-pathological classification system for mesial temporal sclerosis. In: Acta neuropathologica 113 (3), S. 235-244. DOI: 10.1007/s00401-006- 0187-0.
  42. Best, N.; Mitchell, J.; Baimbridge, K. G.; Wheal, H. V. (1993): Changes in parvalbumin-immunoreactive neurons in the rat hippocampus following a kainic acid lesion. In: Neuroscience letters 155 (1), S. 1-6.
  43. Bragin, A.; Wilson, C. L.; Engel, J., JR (2000): Chronic epileptogenesis requires development of a network of pathologically interconnected neuron clusters: a hypothesis. In: Epilepsia 41 Suppl 6, S. S144-52.
  44. Blumcke, Ingmar; Coras, Roland; Miyata, Hajime; Ozkara, Cigdem (2012): Defining cliniconeuropathological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis. In: Brain pathology (Zurich, Switzerland) 22 (3), S. 402-411. DOI: 10.1111/j.1750- 3639.2012.00583.x.
  45. Claassen, J.; Mayer, S. A.; Kowalski, R. G.; Emerson, R. G.; Hirsch, L. J. (2004): Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. In: Neurology 62 (10), S. 1743-1748.
  46. Goddard, G. V. (1967): Development of epileptic seizures through brain stimulation at low intensity. In: Nature 214 (5092), S. 1020-1021.
  47. Del Felice, Alessandra; Beghi, Ettore; Boero, Giovanni; La Neve, Angela; Bogliun, Graziella; Palo, Alessia de; Specchio, Luigi M. (2010): Early versus late remission in a cohort of patients with newly diagnosed epilepsy. In: Epilepsia 51 (1), S. 37-42. DOI: 10.1111/j.1528- 1167.2009.02141.x.
  48. Bernasconi, N.; Bernasconi, A.; Caramanos, Z.; Dubeau, F.; Richardson, J.; Andermann, F.; Arnold, D. L. (2001): Entorhinal cortex atrophy in epilepsy patients exhibiting normal hippocampal volumes. In: Neurology 56 (10), S. 1335-1339.
  49. (1999): Entorhinal cortex in temporal lobe epilepsy: a quantitative MRI study. In: Neurology 52 (9), S. 1870-1876.
  50. Bernasconi, Neda; Andermann, Frederick; Arnold, Douglas L.; Bernasconi, Andrea (2003): Entorhinal cortex MRI assessment in temporal, extratemporal, and idiopathic generalized epilepsy. In: Epilepsia 44 (8), S. 1070-1074.
  51. CDC (2012): Epilepsy in adults and access to care--United States, 2010. In: MMWR. Morbidity and mortality weekly report 61 (45), S. 909-913.
  52. Livingston, R B; French, J D; Richland, K J; Konigsmark, B (1956): Experimental studies on cortical epileptogenesis. In: Transactions of the American Neurological Association (81st Meeting), S. 43-46.
  53. Pitkanen, Asla; Immonen, Riikka J.; Grohn, Olli H. J.; Kharatishvili, Irina (2009): From traumatic brain injury to posttraumatic epilepsy: what animal models tell us about the process and treatment options. In: Epilepsia 50 Suppl 2, S. 21-29. DOI: 10.1111/j.1528- 1167.2008.02007.x.
  54. Bragin, A.; Engel, J., JR; Wilson, C. L.; Fried, I.; Buzsaki, G. (1999): High-frequency oscillations in human brain. In: Hippocampus 9 (2), S. 137-142. DOI: 10.1002/(SICI)1098- 1063(1999)9:2<137::AID-HIPO5>3.0.CO;2-0.
  55. Harvey, Brian D.; Sloviter, Robert S. (2005): Hippocampal granule cell activity and c-Fos expression during spontaneous seizures in awake, chronically epileptic, pilocarpine-treated rats: Insausti, R.; Amaral, D. G.; Cowan, W. M. (1987): The entorhinal cortex of the monkey: II.
  56. Calcagnotto, M. E.; Barbarosie, M.; Avoli, M. (2000): Hippocampus-entorhinal cortex loop and seizure generation in the young rodent limbic system. In: Journal of neurophysiology 83 (5), S. 3183-3187.
  57. Semah, F.; Picot, M. C.; Adam, C.; Broglin, D.; Arzimanoglou, A.; Bazin, B. et al. (1998): Is the underlying cause of epilepsy a major prognostic factor for recurrence? In: Neurology 51 (5), S. 1256-1262.
  58. Dorandeu, Frederic; Barbier, Laure; Dhote, Franck; Testylier, Guy; Carpentier, Pierre (2013): Ketamine combinations for the field treatment of soman-induced self-sustaining status epilepticus. Review of current data and perspectives. In: Chemico-biological interactions 203 (1), S.
  59. McIntyre, Dan C.; Poulter, Michael O.; Gilby, Krista (2002): Kindling: some old and some new. In: Epilepsy Res 50 (1-2), S. 79-92.
  60. Goldberg, Ethan M.; Coulter, Douglas A. (2013): Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction. In: Nature reviews. Neuroscience 14 (5), S. 337-349.
  61. Pitkanen, Asla; Lukasiuk, Katarzyna (2011): Mechanisms of epileptogenesis and potential treatment targets. In: The Lancet. Neurology 10 (2), S. 173-186. DOI: 10.1016/S1474- 4422(10)70310-0.
  62. Racine, R. J. (1972): Modification of seizure activity by electrical stimulation. II. Motor seizure. In: Electroencephalography and clinical neurophysiology 32 (3), S. 281-294.
  63. Deller, T.; Frotscher, M.; Nitsch, R. (1995): Morphological evidence for the sprouting of inhibitory commissural fibers in response to the lesion of the excitatory entorhinal input to the rat dentate gyrus. In: J Neurosci 15 (10), S. 6868-6878.
  64. Jutila, L.; Ylinen, A.; Partanen, K.; Alafuzoff, I.; Mervaala, E.; Partanen, J. et al. (2001): MR volumetry of the entorhinal, perirhinal, and temporopolar cortices in drug-refractory temporal lobe epilepsy. In: AJNR. American journal of neuroradiology 22 (8), S. 1490-1501.
  65. Mullen, R. J.; Buck, C. R.; Smith, A. M. (1992): NeuN, a neuronal specific nuclear protein in vertebrates. In: Development (Cambridge, England) 116 (1), S. 201-211.
  66. Buckmaster, P. S.; Dudek, F. E. (1997): Neuron loss, granule cell axon reorganization, and functional changes in the dentate gyrus of epileptic kainate-treated rats. In: The Journal of comparative neurology 385 (3), S. 385-404.
  67. Deller, Thomas; Bas Orth, Carlos; Vlachos, Andreas; Merten, Tobias; Del Turco, Domenico; Dehn, Doris et al. (2006): Plasticity of synaptopodin and the spine apparatus organelle in the rat fascia dentata following entorhinal cortex lesion. In: J Comp Neurol 499 (3), S. 471-484.
  68. Gorter, J. A.; van Vliet, E. A.; Aronica, E.; Lopes da Silva, F H (2001): Progression of spontaneous seizures after status epilepticus is associated with mossy fibre sprouting and extensive bilateral loss of hilar parvalbumin and somatostatin-immunoreactive neurons. In: The European journal of neuroscience 13 (4), S. 657-669.
  69. Gotman, J. (1984): Relationships between triggered seizures, spontaneous seizures, and interictal spiking in the kindling model of epilepsy. In: Experimental neurology 84 (2), S. 259- 273.
  70. Nadler, J. V.; Perry, B. W.; Cotman, C. W. (1980): Selective reinnervation of hippocampal area CA1 and the fascia dentata after destruction of CA3-CA4 afferents with kainic acid. In: Brain research 182 (1), S. 1-9.
  71. Lorente de Nó, R. (1934): Studies on the structure of the cerebral cortex. Continuation of the study of the ammonic system. In: J. Psychol. Neurol. 46, S. 113-177.
  72. Carmichael, S. Thomas; Chesselet, Marie-Francoise (2002): Synchronous neuronal activity is a signal for axonal sprouting after cortical lesions in the adult. In: The Journal of neuroscience : the official journal of the Society for Neuroscience 22 (14), S. 6062-6070.
  73. Bertram, E. H.; Cornett, J. F. (1994): The evolution of a rat model of chronic spontaneous limbic seizures. In: Brain research 661 (1-2), S. 157-162.
  74. McIntyre, Dan C. (2006): The Kindling Phenomenon. In: Models of Seizures and Epilepsy: Elsevier, S. 351-363.
  75. (1988): The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 96 (10), S. 857-881.
  76. Bertram, E. H.; Cornett, J. (1993): The ontogeny of seizures in a rat model of limbic epilepsy: evidence for a kindling process in the development of chronic spontaneous seizures. In: Brain research 625 (2), S. 295-300.
  77. Bertram, Edward (2007): The relevance of kindling for human epilepsy. In: Epilepsia 48 Suppl 2, S. 65-74.
  78. (1989): Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model.
  79. Gowers, William Richard (1881): Epilepsy and other chronic convulsive diseases : their causes, symptoms, & treatment. London: Churchill. Online verfügbar unter https://archive.org/details/epilepsyotherchr00goweuoft.


* Das Dokument ist im Internet frei zugänglich - Hinweise zu den Nutzungsrechten