Therapeutic Effects of Kv7 Channel Activator Retigabine against Seizures and Neurodegeneration in Kainic Acid-Induced Seizure Model

Therapeutic Effects of Kv7 Channel Activator Retigabine against Seizures and Neurodegeneration in Kainic Acid-Induced Seizure Model

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Author(s)

Author(s): Xiao-fei Zhuang

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DOI: 10.18483/ijSci.2598 9 37 9-14 Volume 11 - Jul 2022

Abstract

Aims: The current study evaluates whether Kv7 channel activator retigabine (RTG) could attenuate seizures and hippocampal neurodegeneration in the kainic acid (KA) induced seizure model. Methods: The anticonvulsant activity of RTG is evaluated by electroencephalography (EEG) recordings in KA-kindled rats. Tunel assay and immunofluorescence of NeuN are used to evaluate the neuroprotective effect of RTG in the hippocampus of KA-kindled rats. Results: RTG effectively reduces epileptiform discharges induced by KA injection. Tunel assay and immunofluorescence of NeuN show that RTG exerts neuroprotection in the hippocampus of KA-kindled rats. Conclusion: Taken together, this study demonstrates that RTG effectively alleviates seizures and hippocampal neurodegeneration in the KA-induced seizure model.

Keywords

Kv7 Channel, RTG, Kainic Acid, Neuroprotection, Seizure

References

  1. Barker-Haliski, M., and Steve White, H. (2020). Validated animal models for antiseizure drug (ASD) discovery: Advantages and potential pitfalls in ASD screening. Neuropharmacology 167, 107750. https://doi.org/10.1016/j.neuropharm.2019.107750
  2. Bear, J., Fountain, N.B., and Lothman, E.W. (1996). Responses of the superficial entorhinal cortex in vitro in slices from naive and chronically epileptic rats. J Neurophysiol 76, 2928-2940. https://doi.org/10.1152/jn.1996.76.5.2928
  3. Bell, B., Lin, J.J., Seidenberg, M., and Hermann, B. (2011). The neurobiology of cognitive disorders in temporal lobe epilepsy. Nat Rev Neurol 7, 154-164. https://doi.org/10.1038/nrneurol.2011.3
  4. Bloss, E.B., and Hunter, R.G. (2010). Hippocampal kainate receptors. Vitam Horm 82, 167-184. https://doi.org/10.1016/s0083-6729(10)82009-6
  5. Boscia, F., Annunziato, L., and Taglialatela, M. (2006). Retigabine and flupirtine exert neuroprotective actions in organotypic hippocampal cultures. Neuropharmacology 51, 283-294. https://doi.org/10.1016/j.neuropharm.2006.03.024
  6. Brown, D.A., and Passmore, G.M. (2009). Neural KCNQ (Kv7) channels. Br J Pharmacol 156, 1185-1195. https://doi.org/10.1111/j.1476-5381.2009.00111.x
  7. Du, F., Eid, T., Lothman, E.W., Köhler, C., and Schwarcz, R. (1995). Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy. J Neurosci 15, 6301-6313. https://doi.org/10.1523/jneurosci.15-10-06301.1995
  8. Fattore, C., and Perucca, E. (2011). Novel medications for epilepsy. Drugs 71, 2151-2178. https://doi.org/10.2165/11594640-000000000-00000
  9. Fernandes, M.J., Carneiro, J.E., Amorim, R.P., Araujo, M.G., and Nehlig, A. (2015). Neuroprotective agents and modulation of temporal lobe epilepsy. Front Biosci (Elite Ed) 7, 79-93. https://doi.org/10.2741/e719
  10. Greene, D.L., and Hoshi, N. (2017). Modulation of Kv7 channels and excitability in the brain. Cell Mol Life Sci 74, 495-508. https://doi.org/10.1007/s00018-016-2359-y
  11. Gunthorpe, M.J., Large, C.H., and Sankar, R. (2012). The mechanism of action of retigabine (ezogabine), a first-in-class K+ channel opener for the treatment of epilepsy. Epilepsia 53, 412-424. https://doi.org/10.1111/j.1528-1167.2011.03365.x
  12. Jimenez-Pacheco, A., Mesuret, G., Sanz-Rodriguez, A., Tanaka, K., Mooney, C., Conroy, R., Miras-Portugal, M.T., Diaz-Hernandez, M., Henshall, D.C., and Engel, T. (2013). Increased neocortical expression of the P2X7 receptor after status epilepticus and anticonvulsant effect of P2X7 receptor antagonist A-438079. Epilepsia 54, 1551-1561. https://doi.org/10.1111/epi.12257
  13. Mora, G., and Tapia, R. (2005). Effects of retigabine on the neurodegeneration and extracellular glutamate changes induced by 4-aminopyridine in rat hippocampus in vivo. Neurochem Res 30, 1557-1565. https://doi.org/10.1007/s11064-005-8834-8
  14. Moshé, S.L., Perucca, E., Ryvlin, P., and Tomson, T. (2015). Epilepsy: new advances. Lancet 385, 884-898. https://doi.org/10.1016/s0140-6736(14)60456-6
  15. Nadler, J.V. (1981). Minireview. Kainic acid as a tool for the study of temporal lobe epilepsy. Life Sci 29, 2031-2042. https://doi.org/10.1016/0024-3205(81)90659-7
  16. Porter, R.J., Nohria, V., and Rundfeldt, C. (2007). Retigabine. Neurotherapeutics : the Journal of the American Society For Experimental NeuroTherapeutics 4, 149-154. https://doi.org/10.1016/j.nurt.2006.11.012
  17. Racine, R.J. (1972). Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32, 281-294. https://doi.org/10.1016/0013-4694(72)90177-0
  18. Singh, T., Mishra, A., and Goel, R.K. (2021). PTZ kindling model for epileptogenesis, refractory epilepsy, and associated comorbidities: relevance and reliability. Metab Brain Dis 36, 1573-1590. https://doi.org/10.1007/s11011-021-00823-3
  19. Smith, M.D., Adams, A.C., Saunders, G.W., White, H.S., and Wilcox, K.S. (2007). Phenytoin- and carbamazepine-resistant spontaneous bursting in rat entorhinal cortex is blocked by retigabine in vitro. Epilepsy Res 74. https://doi.org/10.1016/j.eplepsyres.2007.02.001
  20. Sutula, T., Cascino, G., Cavazos, J., Parada, I., and Ramirez, L. (1989). Mossy fiber synaptic reorganization in the epileptic human temporal lobe. Ann Neurol 26, 321-330. https://doi.org/10.1002/ana.410260303
  21. Tai, X.Y., Bernhardt, B., Thom, M., Thompson, P., Baxendale, S., Koepp, M., and Bernasconi, N. (2018). Review: Neurodegenerative processes in temporal lobe epilepsy with hippocampal sclerosis: Clinical, pathological and neuroimaging evidence. Neuropathol Appl Neurobiol 44, 70-90. https://doi.org/10.1111/nan.12458
  22. Venceslas, D., and Corinne, R. (2017). A Mesiotemporal Lobe Epilepsy Mouse Model. Neurochem Res 42, 1919-1925. https://doi.org/10.1007/s11064-017-2239-3
  23. Vincent, P., and Mulle, C. (2009). Kainate receptors in epilepsy and excitotoxicity. Neuroscience 158, 309-323. https://doi.org/10.1016/j.neuroscience.2008.02.066
  24. Wang, Q., Yu, S., Simonyi, A., Sun, G.Y., and Sun, A.Y. (2005). Kainic acid-mediated excitotoxicity as a model for neurodegeneration. Mol Neurobiol 31, 3-16. https://doi.org/10.1385/mn:31:1-3:003
  25. Weisenberg, J., Wong, M.J.N.d., and treatment (2011). Profile of ezogabine (retigabine) and its potential as an adjunctive treatment for patients with partial-onset seizures. 7, 409-414. https://doi.org/10.2147/ndt.s14208
  26. White, H.J.E. (2003). Preclinical development of antiepileptic drugs: past, present, and future directions. 2-8. https://doi.org/10.1046/j.1528-1157.44.s7.10.x
  27. Wulff, H., Castle, N., and Pardo, L.J.N.r.D.d. (2009). Voltage-gated potassium channels as therapeutic targets. Nature reviews Drug discovery 8, 982-1001. https://doi.org/10.1038/nrd2983

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International Journal of Sciences is Open Access Journal.
This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.
Author(s) retain the copyrights of this article, though, publication rights are with Alkhaer Publications.

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