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Critical Reviews™ in Neurobiology

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ISSN Druckformat: 0892-0915

ISSN Online: 2375-0014

SJR: 0.121

Seizures Beget Seizures: The Quest for GABA as a Key Player

Volumen 18, Ausgabe 1-2, 2006, pp. 135-144
DOI: 10.1615/CritRevNeurobiol.v18.i1-2.140
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ABSTRAKT

Synapses mediated by γ-aminobutyric acid (GABA) A receptors are notoriously altered during periods of enhanced activity. Since a loss of inhibitory tone is a basic cause of seizures and epilepsies, it is important to determine the underlying mechanisms and the way this could be alleviated or at least reduced. Alterations of the intracellular content of chloride are thought to be a major player in the sequence of events that follow episodes of hyperactivity. In this review, I discuss these mechanisms both in the adult and developing brain, relying on studies in which chloride and GABAergic currents were measured by electrophysiological and imaging techniques. The main conclusion is that in adult systems, status epilepticus induces a complete re-organization of the networks, with cell death, axonal growth, and glutamatergic neosynapse formation leading to an increased glutamatergic drive. This, in turn, will decrease the threshold of seizure generation and thus contribute to seizure generation. In contrast, GABAergic synapses are not readily "plastic" as the lost interneurones and synapses are not replaced. Somatostatin-positive 0-LM Interneurons that innervate the dendrites of the principal cells in the hippocampus degenerate selectively, leading to a loss of the inhibitory drive in the dendrites, whereas somatic projecting basket cells and somatic inhibitory drives are relatively spared. This imbalance leads to a reduction of the inhibitory strength that is necessary but not sufficient to generate ongoing seizures. An additional important factor is the persistent increase of the intracellular chloride concentration that leads to a long-lasting shift in the depolarizing direction of the actions of GABA that will also contribute to seizure generation. In the developing brain, a major source of seizure generation is the depolarizing and often excitatory actions of GABA due to a higher intracellular chloride concentration ([Cl]I) in immature neurons, a property that has been confirmed in all developing systems and animal species studied. As a consequence, immature GABAergic synapses will excite targets and facilitate the emergence of seizures, in keeping with the well-known higher incidence of seizures in the developing brain. Using a unique preparation with two intact hippocampi placed in a three-compartment chamber in vitro, we have provided direct evidence that seizures beget seizures and that GABA signaling plays a central role in this phenomenon. Indeed, recurrent seizures triggered in one hippocampus by a convulsive agent propagate to the other hippocampus and transform the naive hippocampus into one that generates seizures once disconnected from the other hippocampus. This transformation is conditioned by the occurrence during the seizures of high-frequency oscillations (40 Hz and above). Interestingly, these oscillations are only produced when N-methyl-D-aspartate (NMDA-) and GABA receptors are operative and not blocked in the naïve hippocampus. Therefore, GABA-receptor antagonists are pro-convulsive in the developing brain but, in fact, anti-epileptic. This paradoxical conclusion has quite a few clinical implications that are discussed.

REFERENZIERT VON
  1. Fisher Robert S., Litt Brian, Stacey William C., Deep Brain Stimulation for Epilepsy, in Youmans Neurological Surgery, 2011. Crossref

  2. Dhir Ashish, Pentylenetetrazol (PTZ) Kindling Model of Epilepsy, Current Protocols in Neuroscience, 58, 1, 2012. Crossref

  3. Egorov Alexei V., Draguhn Andreas, Development of coherent neuronal activity patterns in mammalian cortical networks: Common principles and local hetereogeneity, Mechanisms of Development, 130, 6-8, 2013. Crossref

  4. Greenfield L. John, Molecular mechanisms of antiseizure drug activity at GABAA receptors, Seizure, 22, 8, 2013. Crossref

  5. Osorio Ivan, Frei Mark G., Sornette Didier, Milton John, Lai Ying-Cheng, Epileptic seizures: Quakes of the brain?, Physical Review E, 82, 2, 2010. Crossref

  6. Kitchigina Valentina, Popova Irina, Sinelnikova Victoria, Malkov Anton, Astasheva Elena, Shubina Liubov, Aliev Rubin, Disturbances of septohippocampal theta oscillations in the epileptic brain: Reasons and consequences, Experimental Neurology, 247, 2013. Crossref

  7. Schwartzkroin Philip A., Cellular bases of focal and generalized epilepsies, in Epilepsy, 107, 2012. Crossref

  8. Zaitsev A. V., Classification and function of GABAergic interneurons of the mammalian cerebral cortex, Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology, 7, 4, 2013. Crossref

  9. Lasoń Władysław, Chlebicka Małgorzata, Rejdak Konrad, Research advances in basic mechanisms of seizures and antiepileptic drug action, Pharmacological Reports, 65, 4, 2013. Crossref

  10. Kadriu Bashkim, Guidotti Alessandro, Costa Erminio, Davis John M., Auta James, Acute Imidazenil Treatment after the Onset of DFP-Induced Seizure Is More Effective and Longer Lasting than Midazolam at Preventing Seizure Activity and Brain Neuropathology, Toxicological Sciences, 120, 1, 2011. Crossref

  11. Vignoli Thiago, Nehlig Astrid, Massironi Silvia Gomes, Coimbra Rita de Cássia Sinigaglia, Mazzacoratti Maria da Graça Naffah, Silva Iara Ribeiro, Neto Eduardo Ferreira de Castro, Persike Daniele Suzete, Fernandes Maria José da Silva, Consequences of pilocarpine-induced status epilepticus in immunodeficient mice, Brain Research, 1450, 2012. Crossref

  12. Rattka Marta, Brandt Claudia, Bankstahl Marion, Bröer Sonja, Löscher Wolfgang, Enhanced susceptibility to the GABA antagonist pentylenetetrazole during the latent period following a pilocarpine-induced status epilepticus in rats, Neuropharmacology, 60, 2-3, 2011. Crossref

  13. Whalley BJ, Stephens GJ, Constanti A, Investigation of the effects of the novel anticonvulsant compound carisbamate (RWJ-333369) on rat piriform cortical neurones in vitro, British Journal of Pharmacology, 156, 6, 2009. Crossref

  14. Silbereis John C., Nobuta Hiroko, Tsai Hui-Hsin, Heine Vivi M., McKinsey Gabriel L., Meijer Dimphna H., Howard MacKenzie A., Petryniak Magda A., Potter Gregory B., Alberta John A., Baraban Scott C., Stiles Charles D., Rubenstein John L.R., Rowitch David H., Olig1 Function Is Required to Repress Dlx1/2 and Interneuron Production in Mammalian Brain, Neuron, 81, 3, 2014. Crossref

  15. Osorio Ivan, Frei Mark G., Sornette Didier, Milton John, Pharmaco-resistant seizures: self-triggering capacity, scale-free properties and predictability?, European Journal of Neuroscience, 30, 8, 2009. Crossref

  16. Isayama Ricardo Noboro, Leite Paulo Emilio Correa, Lima Jean Pierre Mendes, Uziel Daniela, Yamasaki Edna Nanami, Impact of Ethanol on the Developing GABAergic System, The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology, 292, 12, 2009. Crossref

  17. Corner Michael A., Spontaneous neuronal burst discharges as dependent and independent variables in the maturation of cerebral cortex tissue cultured in vitro: A review of activity-dependent studies in live ‘model’ systems for the development of intrinsically generated bioelectric slow-wave sleep patterns, Brain Research Reviews, 59, 1, 2008. Crossref

  18. Lachance-Touchette Pamela, Brown Patricia, Meloche Caroline, Kinirons Peter, Lapointe Line, Lacasse Hélène, Lortie Anne, Carmant Lionel, Bedford Fiona, Bowie Derek, Cossette Patrick, Novel α1 and γ2 GABAA receptor subunit mutations in families with idiopathic generalized epilepsy, European Journal of Neuroscience, 34, 2, 2011. Crossref

  19. Di Vito Anna, Giusi Giuseppina, Alò Raffaella, Piscioneri Antonella, Morelli Sabrina, De Bartolo Loredana, Canonaco Marcello, Distinct α GABAAR subunits influence structural and transcriptional properties of CA1 hippocampal neurons, Neuroscience Letters, 496, 2, 2011. Crossref

  20. Shetty Ashok K., Promise of resveratrol for easing status epilepticus and epilepsy, Pharmacology & Therapeutics, 131, 3, 2011. Crossref

  21. Johnston Michael V., Education of a Child Neurologist: Developmental Neuroscience Relevant to Child Neurology, Seminars in Pediatric Neurology, 18, 2, 2011. Crossref

  22. Hattiangady Bharathi, Rao Muddanna S., Shetty Ashok K., Grafting of striatal precursor cells into hippocampus shortly after status epilepticus restrains chronic temporal lobe epilepsy, Experimental Neurology, 212, 2, 2008. Crossref

  23. Ramamoorthi Kartik, Lin Yingxi, The contribution of GABAergic dysfunction to neurodevelopmental disorders, Trends in Molecular Medicine, 17, 8, 2011. Crossref

  24. Nyitrai Gabriella, Lasztóczi Bálint, Kardos Julianna, Glutamate uptake shapes low-[Mg2+] induced epileptiform activity in juvenile rat hippocampal slices, Brain Research, 1309, 2010. Crossref

  25. West P.J., Marcy V.R., Marino M.J., Schaffhauser H., Activation of the 5-HT6 receptor attenuates long-term potentiation and facilitates GABAergic neurotransmission in rat hippocampus, Neuroscience, 164, 2, 2009. Crossref

  26. Megahed Tarick, Hattiangady Bharathi, Shuai Bing, Shetty Ashok K., Parvalbumin and neuropeptide Y expressing hippocampal GABA-ergic inhibitory interneuron numbers decline in a model of Gulf War illness, Frontiers in Cellular Neuroscience, 8, 2015. Crossref

  27. Auvin Stéphane, Porta Natacha, Nehlig Astrid, Lecointe Cécile, Vallée Louis, Bordet Régis, Inflammation in rat pups subjected to short hyperthermic seizures enhances brain long-term excitability, Epilepsy Research, 86, 2-3, 2009. Crossref

  28. Shetty Ashok K., Upadhya Dinesh, GABA-ergic cell therapy for epilepsy: Advances, limitations and challenges, Neuroscience & Biobehavioral Reviews, 62, 2016. Crossref

  29. Xu S., Zhou S., Xia D., Xia J., Chen G., Duan S., Luo J., Defects of synaptic vesicle turnover at excitatory and inhibitory synapses in Niemann–Pick C1-deficient neurons, Neuroscience, 167, 3, 2010. Crossref

  30. Cardoso Armando, Freitas-da-Costa Paulo, Carvalho Liliana S., Lukoyanov Nikolai V., Seizure-induced changes in neuropeptide Y-containing cortical neurons: Potential role for seizure threshold and epileptogenesis, Epilepsy & Behavior, 19, 4, 2010. Crossref

  31. Joensuu Tarja, Tegelberg Saara, Reinmaa Eva, Segerstråle Mikael, Hakala Paula, Pehkonen Heidi, Korpi Esa R., Tyynelä Jaana, Taira Tomi, Hovatta Iiris, Kopra Outi, Lehesjoki Anna-Elina, Gonzalez-Alegre Pedro, Gene Expression Alterations in the Cerebellum and Granule Neurons of Cstb−/− Mouse Are Associated with Early Synaptic Changes and Inflammation, PLoS ONE, 9, 2, 2014. Crossref

  32. Yang Libai, Cai Xiaodong, Zhou Jueqian, Chen Shuda, Chen Yishu, Chen Ziyi, Wang Qian, Fang Ziyan, Zhou Liemin, Duan Shumin, STE20/SPS1-Related Proline/Alanine-Rich Kinase Is Involved in Plasticity of GABA Signaling Function in a Mouse Model of Acquired Epilepsy, PLoS ONE, 8, 9, 2013. Crossref

  33. Maffei Arianna, The Many Forms and Functions of Long Term Plasticity at GABAergic Synapses, Neural Plasticity, 2011, 2011. Crossref

  34. Zhao Jianghao, Tao Hua, Xian Wenchuan, Cai Yujie, Cheng Wanwen, Yin Mingkang, Liang Guocong, Li Keshen, Cui Lili, Zhao Bin, A Highly Selective Inhibitor of Glycine Transporter-1 Elevates the Threshold for Maximal Electroshock-Induced Tonic Seizure in Mice, Biological & Pharmaceutical Bulletin, 39, 2, 2016. Crossref

  35. Kuruba Ramkumar, Hattiangady Bharathi, Parihar Vipan K., Shuai Bing, Shetty Ashok K., Borlongan Cesario V., Differential Susceptibility of Interneurons Expressing Neuropeptide Y or Parvalbumin in the Aged Hippocampus to Acute Seizure Activity, PLoS ONE, 6, 9, 2011. Crossref

  36. Alvarez Dolado Manuel, Broccoli Vania, GABAergic Neuronal Precursor Grafting: Implications in Brain Regeneration and Plasticity, Neural Plasticity, 2011, 2011. Crossref

  37. Fabiano Valentina, Mameli Chiara, Zuccotti Gian Vincenzo, Adverse drug reactions in newborns, infants and toddlers: pediatric pharmacovigilance between present and future, Expert Opinion on Drug Safety, 11, 1, 2012. Crossref

  38. Zarnadze Shota, Bäuerle Peter, Santos-Torres Julio, Böhm Claudia, Schmitz Dietmar, Geiger Jörg RP, Dugladze Tamar, Gloveli Tengis, Cell-specific synaptic plasticity induced by network oscillations, eLife, 5, 2016. Crossref

  39. Walker Jeffrey, Storch Gregory, Quach-Wong Bonnie, Sonnenfeld Julian, Aaron Gloster, Brown Jon T., Propagation of Epileptiform Events across the Corpus Callosum in a Cingulate Cortical Slice Preparation, PLoS ONE, 7, 2, 2012. Crossref

  40. Wendling F., Gerber U., Cosandier-Rimele D., Nica A., De Montigny J., Raineteau O., Kalitzin S., Lopes da Silva F., Benquet P., Brain (Hyper)Excitability Revealed by Optimal Electrical Stimulation of GABAergic Interneurons, Brain Stimulation, 9, 6, 2016. Crossref

  41. Shao Hui, Yang Yang, Mi Ze, Zhu Guang-xi, Qi Ai-ping, Ji Wei-gang, Zhu Zhi-ru, Anticonvulsant effect of Rhynchophylline involved in the inhibition of persistent sodium current and NMDA receptor current in the pilocarpine rat model of temporal lobe epilepsy, Neuroscience, 337, 2016. Crossref

  42. Nomura Sadahiro, Inoue Takao, Imoto Hirochika, Suehiro Eiichi, Maruta Yuichi, Hirayama Yuya, Suzuki Michiyasu, Effects of focal brain cooling on extracellular concentrations of neurotransmitters in patients with epilepsy, Epilepsia, 58, 4, 2017. Crossref

  43. Singer Philipp, Yee Benjamin K., Pharmacotherapy Through the Inhibition of Glycine Transporters: An Update on and Beyond Schizophrenia, in Psychiatry and Neuroscience Update - Vol. II, 2017. Crossref

  44. Wittner Lucia, Maglóczky Zsófia, Synaptic Reorganization of the Perisomatic Inhibitory Network in Hippocampi of Temporal Lobe Epileptic Patients, BioMed Research International, 2017, 2017. Crossref

  45. Kirischuk Sergei, Sinning Anne, Blanquie Oriane, Yang Jenq-Wei, Luhmann Heiko J., Kilb Werner, Modulation of Neocortical Development by Early Neuronal Activity: Physiology and Pathophysiology, Frontiers in Cellular Neuroscience, 11, 2017. Crossref

  46. Zaitsev A. V., The Role of GABAergic Interneurons in the Cortex and Hippocampus in the Development of Epilepsy, Neuroscience and Behavioral Physiology, 47, 8, 2017. Crossref

  47. Godoy Lívea, Liberato José, Celani Marcus, Gobbo-Neto Leonardo, Lopes Norberto, dos Santos Wagner, Disease Modifying Effects of the Spider Toxin Parawixin2 in the Experimental Epilepsy Model, Toxins, 9, 9, 2017. Crossref

  48. Gulyaeva N. V., Staging of neuroplasticity alterations during epileptogenesis (temporal lobe epileply as an example), Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova, 117, 9, 2017. Crossref

  49. Gauvin David V., Zimmermann Zachary J., Yoder Joshua, Harter Marci, Holdsworth David, Kilgus Quinn, May Jonelle, Dalton Jill, Baird Theodore J., A predictive index of biomarkers for ictogenesis from tier I safety pharmacology testing that may warrant tier II EEG studies, Journal of Pharmacological and Toxicological Methods, 94, 2018. Crossref

  50. Schulte Joran T., Wierenga Corette J., Bruining Hilgo, Chloride transporters and GABA polarity in developmental, neurological and psychiatric conditions, Neuroscience & Biobehavioral Reviews, 90, 2018. Crossref

  51. Butler Kameryn M, Moody Olivia A, Schuler Elisabeth, Coryell Jason, Alexander John J, Jenkins Andrew, Escayg Andrew, De novo variants in GABRA2 and GABRA5 alter receptor function and contribute to early-onset epilepsy, Brain, 141, 8, 2018. Crossref

  52. Shmakova Anna A., Rubina Kseniya A., Rysenkova Karina D., Gruzdeva Anna M., Ivashkina Olga I., Anokhin Konstantin V., Tkachuk Vsevolod A., Semina Ekaterina V., Urokinase receptor and tissue plasminogen activator as immediate‐early genes in pentylenetetrazole‐induced seizures in the mouse brain, European Journal of Neuroscience, 51, 7, 2020. Crossref

  53. Keck Tara, White John A., Glycinergic Inhibition in the Hippocampus, Reviews in the Neurosciences, 20, 1, 2009. Crossref

  54. Nadler J. Victor, Spencer Dennis D., What Is a Seizure Focus?, in Issues in Clinical Epileptology: A View from the Bench, 813, 2014. Crossref

  55. Billakota Santoshi, Devinsky Orrin, Kim Kyung-Wha, Why we urgently need improved epilepsy therapies for adult patients, Neuropharmacology, 170, 2020. Crossref

  56. Jones-Davis Dorothy, Calcagnotto Maria-Elisa, Sebe Joy Y., Interneuron Loss as a Cause of Seizures: Lessons from Interneuron-Deficient Mice, in Animal Models of Epilepsy, 40, 2009. Crossref

  57. Li Rong, Wu Bing, He Miaoqing, Zhang Peng, Zhang Qinbin, Deng Jing, Yuan Jinxian, Chen Yangmei, HAP1 Modulates Epileptic Seizures by Regulating GABAAR Function in Patients with Temporal Lobe Epilepsy and in the PTZ-Induced Epileptic Model, Neurochemical Research, 45, 9, 2020. Crossref

  58. Han Wenyan, Shepard Ryan D., Lu Wei, Regulation of GABAARs by Transmembrane Accessory Proteins, Trends in Neurosciences, 44, 2, 2021. Crossref

  59. Shen Yujia, Gong Yiwei, Ruan Yeping, Chen Zhong, Xu Cenglin, Secondary Epileptogenesis: Common to See, but Possible to Treat?, Frontiers in Neurology, 12, 2021. Crossref

  60. Godoy Lívea Dornela, Prizon Tamiris, Rossignoli Matheus Teixeira, Leite João Pereira, Liberato José Luiz, Parvalbumin Role in Epilepsy and Psychiatric Comorbidities: From Mechanism to Intervention, Frontiers in Integrative Neuroscience, 16, 2022. Crossref

  61. Baek Je-Hyun, Rubinstein Moran, Scheuer Todd, Trimmer James S., Reciprocal Changes in Phosphorylation and Methylation of Mammalian Brain Sodium Channels in Response to Seizures, Journal of Biological Chemistry, 289, 22, 2014. Crossref

  62. Cavalcante Bruno Raphael Ribeiro, Improta-Caria Alex Cleber, Melo Victor Hugo de, De Sousa Ricardo Augusto Leoni, Exercise-linked consequences on epilepsy, Epilepsy & Behavior, 121, 2021. Crossref

  63. Lin Daisy, Liu Jinyang, Florveus Alizna, Ganesan Vanathi, Cottrell James E., Kass Ira S., Exposure to Sevoflurane, But Not Ketamine, During Early-life Brain Development has Long-Lasting Effects on GABAA Receptor Mediated Inhibitory Neurotransmission, Neuroscience, 472, 2021. Crossref

  64. Introduction, in The Causes of Epilepsy, 2011. Crossref

  65. Schwartzkroin Philip A., Mechanisms of epileptogenesis in symptomatic epilepsy, in The Causes of Epilepsy, 2011. Crossref

  66. Zhou Rong, Bai Yinyang, Yang Rong, Zhu Ying, Chi Xia, Li Lin, Chen Lei, Sokabe Masahiro, Chen Ling, Abnormal synaptic plasticity in basolateral amygdala may account for hyperactivity and attention-deficit in male rat exposed perinatally to low-dose bisphenol-A, Neuropharmacology, 60, 5, 2011. Crossref

  67. Shrivastava Sushant Kumar, Sinha Ojaswi, Kumar Munish, Waiker Digambar Kumar, Verma Akash, Tripathi Prabhash Nath, Bhardwaj Bhagwati, Saraf Poorvi, Synthesis, characterization, and biological evaluation of some novel ϒ-aminobutyric acid aminotransferase (GABA-AT) inhibitors, Medicinal Chemistry Research, 31, 9, 2022. Crossref

  68. Chakraborty Sukanya, Parayil Rrejusha, Mishra Shefali, Nongthomba Upendra, Clement James P., Epilepsy Characteristics in Neurodevelopmental Disorders: Research from Patient Cohorts and Animal Models Focusing on Autism Spectrum Disorder, International Journal of Molecular Sciences, 23, 18, 2022. Crossref

  69. Arai Naohiro, Miyazaki Takahiro, Nakajima Shinichiro, Okamoto Shun, Moriyama Sotaro, Niinomi Kanta, Takayama Kousuke, Kato Jungo, Nakamura Itta, Hirano Yoji, Kitago Minoru, Kitagawa Yuko, Takahashi Tatsuo, Shimizu Hideyuki, Mimura Masaru, Noda Yoshihiro, The Association between Electroencephalography with Auditory Steady-State Response and Postoperative Delirium, Journal of Personalized Medicine, 13, 1, 2022. Crossref

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