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Neurochemical Research

, Volume 42, Issue 10, pp 2730–2742 | Cite as

Phase-Dependent Astroglial Alterations in Li–Pilocarpine-Induced Status Epilepticus in Young Rats

  • Adriana Fernanda K. VizueteEmail author
  • Matheus Mittmann Hennemann
  • Carlos Alberto Gonçalves
  • Diogo Losch de Oliveira
Original Paper

Abstract

Epilepsy prevalence is high in infancy and in the elderly population. Lithium–pilocarpine is widely used to induce experimental animal models of epilepsy, leading to similar neurochemical and morphological alterations to those observed in temporal lobe epilepsy. As astrocytes have been implicated in epileptic disorders, we hypothesized that specific astroglial changes accompany and contribute to epileptogenesis. Herein, we evaluated time-dependent astroglial alterations in the hippocampus of young (27-day-old) rats at 1, 14 and 56 days after Li–pilocarpine-induced status epilepticus (SE), corresponding to different phases in this model of epilepsy. We determined specific markers of astroglial activation: GFAP, S100B, glutamine synthetase (GS), glutathione (GSH) content, aquaporin-4 (AQP-4) and potassium channel Kir 4.1; as well as epileptic behavioral, inflammatory and neurodegenerative changes. Phase-dependent signs of hippocampal astrogliosis were observed, as demonstrated by increments in GFAP, S100B and GS. Astrocyte dysfunction in the hippocampus was characterized, based on the decrease in GSH content, AQP-4 and Kir 4.1 channels. Degenerating neurons were identified by Fluoro-Jade C staining. We found a clear, early (at SE1) and persistent (at SE56) increase in cerebrospinal fluid (CSF) S100B levels. Additionally, serum S100B was found to decrease soon after SE induction, implicating a rapid-onset increase in the CSF/serum S100B ratio. However, serum S100B increased at SE14, possibly reflecting astroglial activation and/or long-term increase in cerebrovascular permeability. Moreover, we suggest that peripheral S100B levels may represent a useful marker for SE in young rats and for follow up during the chronic phases of this model of epilepsy. Together, results reinforce and extend the idea of astroglial involvement in epileptic disorders.

Keywords

Astrocyte dysfunction Astrogliosis Epilepsy Pilocarpine S100B 

Notes

Acknowledgements

This study was supported by the National Council for Scientific and Technological Development (CNPq, Brazil), Ministry of Education (MEC/CAPES, Brazil), State Foundation for Scientific Research of Rio Grande do Sul (FAPERGS), National Institute of Science and Technology for Excitotoxicity and Neuroprotection (MCT/INCTEN), and project CNPq 27/2014-Neurodegenerative diseases.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interests.

Supplementary material

Videomonitoring of SE animals between 1 and 8 weeks after pilocarpine injection. Animal development scores of 2 or 3, Racine scale. (MPG 90304 KB)

References

  1. 1.
    Banerjee PN et al (2009) The descriptive epidemiology of epilepsy-a review. Epilepsy Res 85:31–45. doi: 10.1016/j.eplepsyres.2009.03.003 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Sander JW (2003) The epidemiology of epilepsy revisited. Curr Opin Neurobiol. doi: 10.1097/01.wco.0000063766.15877.8e Google Scholar
  3. 3.
    Schmidt D, Wolfgang L (2005) Drug resistance in epilepsy: putative neurobiologic and clinical mechanisms. Epilepsia 46:858–877CrossRefPubMedGoogle Scholar
  4. 4.
    Cavalheiro EA, Leite JP, Bortolotto ZA et al (1991) Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia 32:778–782. doi: 10.1111/j.1528-1157.1991.tb05533.x CrossRefPubMedGoogle Scholar
  5. 5.
    Turski WA, Cavalheiro EA, Schwarz M et al (1983) Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study. Behav Brain Res 9:315–335. doi: 10.1016/0166-4328(83)90136-5 CrossRefPubMedGoogle Scholar
  6. 6.
    Nehlig A, Koning E (2002) Status epilepticus induced by lithium-pilocarpine in the immature rat does not change the long-term susceptibility to seizures. Epilepsy Res 51:189–197CrossRefPubMedGoogle Scholar
  7. 7.
    Goffin K, Nissinen J, Van Laere K, Pitkänen A (2007) Cyclicity of spontaneous recurrent seizures in pilocarpine model of temporal lobe epilepsy in rat. Exp Neurol 205:501–505. doi: 10.1016/j.expneurol.2007.03.008 CrossRefPubMedGoogle Scholar
  8. 8.
    Castro OW, Furtado MA, Tilelli CQ et al (2010) Comparative neuroanatomical and temporal characterization of FluoroJade-positive neurodegeneration after status epilepticus induced by systemic and intrahippocampal pilocarpine in Wistar rats. Brain Res 1374:43–55. doi: 10.1016/j.brainres.2010.12.012 CrossRefPubMedGoogle Scholar
  9. 9.
    Wang L, Liu Y, Huang Y, Chen L (2008) Time-course of neuronal death in the mouse pilocarpine model of chronic epilepsy using Fluoro-Jade C staining. Brain Res. doi: 10.1016/j.brainres.2008.07.097 Google Scholar
  10. 10.
    Auvin S, Mazarati A, Shin D, Sankar R (2010) Inflammation enhances epileptogenesis in the developing rat brain. Neurobiol Dis 40:303–310. doi: 10.1016/j.nbd.2010.06.004 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    de Oliveira DL, Fischer A, Jorge RS et al (2008) Effects of early-life LiCl-pilocarpine-induced status epilepticus on memory and anxiety in adult rats are associated with mossy fiber sprouting and elevated CSF S100B protein. Epilepsia 49:842–852. doi: 10.1111/j.1528-1167.2007.01484.x CrossRefPubMedGoogle Scholar
  12. 12.
    Shapiro LA, Wang L, Ribak CE (2008) Rapid astrocyte and microglial activation following pilocarpine-induced seizures in rats. Epilepsia 49:33–41. doi: 10.1111/j.1528-1167.2008.01491.x CrossRefPubMedGoogle Scholar
  13. 13.
    Seifert G, Steinhäuser C (2013) Neuron–astrocyte signaling and epilepsy. Exp Neurol. doi: 10.1016/j.expneurol.2011.08.024 PubMedGoogle Scholar
  14. 14.
    Zhu W, Zhang S, Feng B et al (2012) Reactive astrocytes contribute to increased epileptic susceptibility induced by subthreshold dose of pilocarpine. Epilepsy Behav 25:426–430. doi: 10.1016/j.yebeh.2012.08.023 CrossRefPubMedGoogle Scholar
  15. 15.
    Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32:421–431. doi: 10.1016/j.tins.2009.05.001 CrossRefPubMedGoogle Scholar
  16. 16.
    Pellerin L, Bouzier-Sore A-K, Aubert A et al (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55:1251–1262. doi: 10.1002/glia.20528 CrossRefPubMedGoogle Scholar
  17. 17.
    Roberta A, Rossella B (2010) Aquaporins and glia. Curr Neuropharmacol 8:84–91CrossRefGoogle Scholar
  18. 18.
    Butt AM, Kalsi A (2006) Inwardly rectifying potassium channels (Kir) in central nervous system glia: a special role for Kir4.1 in glial functions. J Cell Mol Med 10:33–44. doi: 10.1111/j.1582-4934.2006.tb00289.x CrossRefPubMedGoogle Scholar
  19. 19.
    Dringen R, Hirrlinger J (2003) Glutathione pathways in the brain. Biol Chem 384:505–516. doi: 10.1515/BC.2003.059 CrossRefPubMedGoogle Scholar
  20. 20.
    Anlauf E, Derouiche A (2013) Glutamine synthetase as an astrocytic marker: its cell type and vesicle localization. Front Endocrinol 4:1–5. doi: 10.3389/fendo.2013.00144 CrossRefGoogle Scholar
  21. 21.
    Arisi GM, Ruch M, Foresti ML et al (2011) Astrocyte alterations in the hippocampus following pilocarpine-induced seizures in aged rats. Aging Dis 2:294–300PubMedPubMedCentralGoogle Scholar
  22. 22.
    Nobili P, Colciaghi F, Finardi A et al (2015) Neurobiology of disease continuous neurodegeneration and death pathway activation in neurons and glia in an experimental model of severe chronic epilepsy. Neurobiol Dis 83:54–66. doi: 10.1016/j.nbd.2015.08.002 CrossRefPubMedGoogle Scholar
  23. 23.
    Clasadonte J, Morel L, Barrios-camacho CM et al (2016) Molecular analysis of acute and chronic reactive astrocytes in the pilocarpine model of temporal lobe epilepsy. Neurobiol Dis 91:315–325. doi: 10.1016/j.nbd.2016.03.024 CrossRefPubMedGoogle Scholar
  24. 24.
    Eid T, Ghosh A, Beckstro H et al (2008) Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats. Brain 131:2061–2070. doi: 10.1093/brain/awn133 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Van Der Hel WS (2005) Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy. Neurology 64:326–333. doi: 10.1212/01.WNL.0000149636.44660.99 CrossRefPubMedGoogle Scholar
  26. 26.
    Freitas RM, Fonteles MMF (2005) Oxidative stress in the hippocampus after pilocarpine-induced status epilepticus in Wistar rats. FEBS J 272:1307–1312. doi: 10.1111/j.1742-4658.2004.04537.x CrossRefPubMedGoogle Scholar
  27. 27.
    Lee DJ, Hsu MS, Seldin MM et al (2012) Decreased expression of the glial water channel aquaporin-4 in the intrahippocampal kainic acid model of epileptogenesis. Exp Neurol 235:246–255. doi: 10.1016/j.expneurol.2012.02.002 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Ravizza T, Rizzi M, Perego C et al (2005) Inflammatory response and glia activation in developing rat hippocampus after status epilepticus. Epilepsia 46:113–117CrossRefPubMedGoogle Scholar
  29. 29.
    Somera-Molina KC, Robin B, Somera CA et al (2007) Glial activation links early-life seizures and long-term neurologic dysfunction: evidence using a small molecule inhibitor of proinflammatory cytokine upregulation. Epilepsia 48:1785–1800. doi: 10.1111/j.1528-1167.2007.01135.x CrossRefPubMedGoogle Scholar
  30. 30.
    Andersen SL (2002) Changes in the second messenger cyclic AMP during development may underlie motoric symptoms in attention deficit/hyperactivity disorder (ADHD). Behav Brain Res 130:197–201CrossRefPubMedGoogle Scholar
  31. 31.
    Engelhardt B (2003) Development of the blood-brain barrier. Cell Tissue Res 119–129. doi: 10.1007/s00441-003-0751-z Google Scholar
  32. 32.
    Nehlig A, Vasconcelos AP De, Boyet S (1989) Postnatal changes in local cerebral blood flow measured by the quantitative autoradiographic [14C] iodoantipyrine technique in freely moving rats. J Cereb Blood Flow Metab 579–588Google Scholar
  33. 33.
    Ben-Ari Y (2002) Excitatory actions of GABA during development: the nature of the nurture. Nat Rev Neurosci 3:728–739. doi: 10.1038/nrn920 CrossRefPubMedGoogle Scholar
  34. 34.
    Lüttjohann A, Fabene PF, Van Luijtelaar G (2009) A revised Racine ’ s scale for PTZ-induced seizures in rats. Physiol Behav 98:579–586. doi: 10.1016/j.physbeh.2009.09.005 CrossRefPubMedGoogle Scholar
  35. 35.
    Leite JP, Garcia-cairasco N, Ca EA (2002) New insights from the use of pilocarpine and kainate models. Epilepsy Res 50:93–103CrossRefPubMedGoogle Scholar
  36. 36.
    Scorza FA, Arida RM, Naffah-Mazzacoratti MG et al (2009) The pilocarpine model of epilepsy: what have we learned? Ann Braz Acad Sci 81:345–365CrossRefGoogle Scholar
  37. 37.
    Leite MC, Galland F, Brolese G et al (2008) A simple, sensitive and widely applicable ELISA for S100B: methodological features of the measurement of this glial protein. J Neurosci Methods 169:93–99. doi: 10.1016/j.jneumeth.2007.11.021 CrossRefPubMedGoogle Scholar
  38. 38.
    Tramontina F, Leite MC, Cereser K et al (2007) Immunoassay for glial fibrillary acidic protein: antigen recognition is affected by its phosphorylation state. J Neurosci Methods 162:282–286. doi: 10.1016/j.jneumeth.2007.01.001 CrossRefPubMedGoogle Scholar
  39. 39.
    Minet R, Villie F, Marcollet M et al (1997) Measurement of glutamine synthetase activity in rat muscle by a colorimetric assay. Clin Chim Acta 268:121–132. doi: 10.1016/S0009-8981(97)00173-3 CrossRefPubMedGoogle Scholar
  40. 40.
    Peterson GL (1977) A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83:346–356. doi: 10.1016/0003-2697(77)90043-4 CrossRefPubMedGoogle Scholar
  41. 41.
    Scholl EA, Dudek FE, Ekstrand JJ (2013) Neuronal degeneration is observed in multiple regions outside the hippocampus after lithium pilocarpine-induced status epilepticus in the immature rat. Neuroscience 252:45–59. doi: 10.1016/j.neuroscience.2013.07.045 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    De Vries EE, Munckhof B Van Den, Braun KPJ et al (2016) Neuroscience and biobehavioral reviews inflammatory mediators in human epilepsy: a systematic review and meta-analysis. Neurosci Biobehav Rev 63:177–190. doi: 10.1016/j.neubiorev.2016.02.007 CrossRefPubMedGoogle Scholar
  43. 43.
    Marchi N, Oby E, Batra A et al (2007) Invivo and invitro effects of pilocarpine: relevance to ictogenesis. Epilepsia 48:1934–1946. doi: 10.1111/j.1528-1167.2007.01185.x CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Freeling J, Wattier K, Lacroix C, Li Y (2007) Neostigmine and pilocarpine attenuated tumour necrosis factor α expression and cardiac hypertrophy in the heart with pressure overload. Exp Physiol 75–82. doi: 10.1113/expphysiol.2007.039784 PubMedGoogle Scholar
  45. 45.
    Altavilla D, Guarini S, Bitto A et al (2006) Activation of the cholinergic anti-inflammatory pathway reduces NF-KB activation, blunts TNF-α production, and protects against splanchnic artery occlusion shock. Shock 25:500–506. doi: 10.1097/01.shk.0000209539.91553.82 CrossRefPubMedGoogle Scholar
  46. 46.
    Welser-alves JV, Milner R (2013) Microglia are the major source of TNF-a and TGF-B in postnatal glial cultures; regulation by cytokines, lipopolysaccharide, and vibronectin. Neurochem Int 63:1–16. doi: 10.1016/j.neuint.2013.04.007.Microglia CrossRefGoogle Scholar
  47. 47.
    Pernot F, Carpentier P, Heinrich C et al (2011) Inflammatory changes during epileptogenesis and spontaneous seizures in a mouse model of mesiotemporal lobe epilepsy. Epilepsia 52:2315–2325. doi: 10.1111/j.1528-1167.2011.03273.x CrossRefPubMedGoogle Scholar
  48. 48.
    Voutsinos-porche B, Koning E, Ferrandon A et al (2004) Temporal patterns of the cerebral inflammatory response in the rat lithium–pilocarpine model of temporal lobe epilepsy. Neurobiol Dis 17:385–402. doi: 10.1016/j.nbd.2004.07.023 CrossRefPubMedGoogle Scholar
  49. 49.
    De Simoni MG, Perego C, Ravizza T et al (2000) Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur J Neurosci 12:2623–2633CrossRefPubMedGoogle Scholar
  50. 50.
    Teocchi MA, Ferreira AÉD, de Oliveira EPDL et al (2013) Hippocampal gene expression dysregulation of Klotho, nuclear factor kappa B and tumor necrosis factor in temporal lobe epilepsy patients. J Neuroinflamm 10:1–7CrossRefGoogle Scholar
  51. 51.
    Castillo-Ruiz MM, Campuzano O, Acarin L et al (2007) Delayed neurodegeneration and early astrogliosis after excitotoxicity to the aged brain. Exp Gerontol 42:343–354. doi: 10.1016/j.exger.2006.10.008 CrossRefPubMedGoogle Scholar
  52. 52.
    Nascimento D (2012) Neuronal degeneration and gliosis time-course in the mouse hippocampal formation after pilocarpine-induced status epilepticus. Brain Res 1470:98–110. doi: 10.1016/j.brainres.2012.06.008 CrossRefPubMedGoogle Scholar
  53. 53.
    Pickering M, Cumiskey D, Connor JJO (2005) Actions of TNF-α on glutamatergic synaptic transmission in the central nervous system. Exp Physiol 90:663–670. doi: 10.1113/expphysiol.2005.030734 CrossRefPubMedGoogle Scholar
  54. 54.
    Zhu W, Zheng H, Shao X et al (2010) Excitotoxicity of TNFalpha derived from KA activated microglia on hippocampal neurons in vitro and in vivo. J Neurochem 114:386–396. doi: 10.1111/j.1471-4159.2010.06763.x CrossRefPubMedGoogle Scholar
  55. 55.
    Poirier JL, Koninck YDE (2000) Differential progression of dark neuron and fluoro-jade labelling in the rat hippocampus following pilocarpine-induced status epilepticus. Neuroscience 97:59–68CrossRefPubMedGoogle Scholar
  56. 56.
    Druga R, Mare P, Kubová H (2010) Time course of neuronal damage in the hippocampus following lithium-pilocarpine status epilepticus in 12-day-old rats. Brain Res 13555:174–179. doi: 10.1016/j.brainres.2010.07.072 CrossRefGoogle Scholar
  57. 57.
    Griffin WS, Yeralan O, Sheng JG et al (1995) Overexpression of the neurotrophic cytokine S100 beta in human temporal lobe epilepsy. J Neurochem 65:228–233CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Rocha E, Achaval M, Santos P, Ca RR (1998) Lithium treatment causes gliosis and modifies the morphology of hippocampal astrocytes. Neuropharmacology 9:3971–3974Google Scholar
  59. 59.
    Ramos AJ, Rossi AR, Angelo MF, Villarreal A (2013) Gabapentin administration reduces reactive gliosis and neurodegeneration after pilocarpine-induced status epilepticus. PLoS ONE. doi: 10.1371/journal.pone.0078516 Google Scholar
  60. 60.
    Donato R, Sorci G, Riuzzi F et al (2009) S100B’s double life: intracellular regulator and extracellular signal. Biochim Biophys Acta 1793:1008–1022. doi: 10.1016/j.bbamcr.2008.11.009 CrossRefPubMedGoogle Scholar
  61. 61.
    Gonçalves CA, Concli Leite M, Nardin P (2008) Biological and methodological features of the measurement of S100B, a putative marker of brain injury. Clin Biochem 41:755–763. doi: 10.1016/j.clinbiochem.2008.04.003 CrossRefPubMedGoogle Scholar
  62. 62.
    de Souza DF, Wartchow K, Hansen F et al (2013) Interleukin-6-induced S100B secretion is inhibited by haloperidol and risperidone. Prog Neuro-Psychopharmacol Biol Psychiat 43:14–22. doi: 10.1016/j.pnpbp.2012.12.001 CrossRefGoogle Scholar
  63. 63.
    Guerra MC, Tortorelli LS, Galland F et al (2011) Lipopolysaccharide modulates astrocytic S100B secretion: a study in cerebrospinal fluid and astrocyte cultures from rats. J Neuroinflamm 8:128. doi: 10.1186/1742-2094-8-128 CrossRefGoogle Scholar
  64. 64.
    Schaefer L (2014) Complexity of danger: the diverse nature of damage-associated molecular patterns. J Biol Chem 289:35237–35245. doi: 10.1074/jbc.R114.619304 CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Sorci G, Bianchi R, Riuzzi F et al (2010) S100B protein, a damage-associated molecular pattern protein in the brain and heart, and beyond. Cardiovasc Psychiatr Neurol. doi: 10.1155/2010/656481 Google Scholar
  66. 66.
    Maroso M, Balosso S, Ravizza T et al (2010) Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat Med 16:413–419. doi: 10.1038/nm.2127 CrossRefPubMedGoogle Scholar
  67. 67.
    Kleindienst A, Meissner S, Eyupoglu IY, Parsch H, Schmidt C BM (2010) Dynamics of S100B release into serum and cerebrospinal fluid following acute brain injury. Acta Neurochir 106:247–250CrossRefGoogle Scholar
  68. 68.
    Kleindienst A et al (2010) The passage of S100B from brain to blood is not specifically related to the blood-brain barrier integrity. Cardiovasc Psychiatr Neurol. doi: 10.1155/2010/801295 Google Scholar
  69. 69.
    Gonçalves CA, Leite MC, Guerra MC (2010) Adipocytes as an important source of serum S100B and possible roles of this protein in adipose tissue. Cardiovasc Psychiatr Neurol 2010:790431. doi: 10.1155/2010/790431 CrossRefGoogle Scholar
  70. 70.
    Friedman A, Kaufer D, Heinemann U (2009) Blood–brain barrier breakdown-inducing astrocytic transformation: Novel targets for the prevention of epilepsy. Epilepsy Res 85:142–149. doi: 10.1016/j.eplepsyres.2009.03.005 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Milesi S, Boussadia B, Plaud C et al (2015) Redistribution of PDGFRβ cells and NG2DsRed pericytes at the cerebrovasculature after status epilepticus. Neurobiol Dis 71:151–158. doi: 10.1016/j.nbd.2014.07.010 CrossRefGoogle Scholar
  72. 72.
    Gorter JA, Van Vliet EA, Aronica E (2015) Status epilepticus, blood–brain barrier disruption, inflammation, and epileptogenesis. Epilepsy Behav 49:13–16. doi: 10.1016/j.yebeh.2015.04.047 CrossRefPubMedGoogle Scholar
  73. 73.
    Löffler D, Landgraf K, Antje K et al (2016) Modulation of triglyceride accumulation in adipocytes by psychopharmacological agents in vitro. J Psych Res 72:37–42. doi: 10.1016/j.jpsychires.2015.10.008 CrossRefGoogle Scholar
  74. 74.
    Eid T, Thomas MJ, Spencer DD et al (2004) Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Lancet 363:28–37CrossRefPubMedGoogle Scholar
  75. 75.
    Dickinson DA, Forman HJ (2002) Cellular glutathione and thiols metabolism. Biochem Pharmacol 64:1019–1026. doi: 10.1016/S0006-2952(02)01172-3 CrossRefPubMedGoogle Scholar
  76. 76.
    Mueller SG, Trabesinger a H, Boesiger P, Wieser HG (2001) Brain glutathione levels in patients with epilepsy measured by in vivo (1)H-MRS. Neurology 57:1422–1427CrossRefPubMedGoogle Scholar
  77. 77.
    Kim J, Ryu HJ, Yeo S, Seo CH (2009) Differential expressions of aquaporin subtypes in astroglia in the hippocampus of chronic epileptic rats. Neuroscience 163:781–789. doi: 10.1016/j.neuroscience.2009.07.028 CrossRefPubMedGoogle Scholar
  78. 78.
    Hubbard JA, Szu JI, Yonan JM, Binder DK (2016) Regulation of astrocyte glutamate transporter-1 (GLT1) and aquaporin-4 (AQP4) expression in a model of epilepsy. Exp Neurol 283:85–96. doi: 10.1016/j.expneurol.2016.05.003 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Strohschein S, Uttmann KH, Gabriel S, Binder DK (2011) Impact of aquaporin-4 channels on K 1 buffering and gap junction coupling in the hippocampus. Glia 980:973–980. doi: 10.1002/glia.21169 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Adriana Fernanda K. Vizuete
    • 1
    Email author
  • Matheus Mittmann Hennemann
    • 1
  • Carlos Alberto Gonçalves
    • 1
  • Diogo Losch de Oliveira
    • 1
  1. 1.Department of Biochemistry, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil

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