Spike-Wave Seizures in WAG/Rij Rat: Baseline and Dexmedetomidine
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  • Release Date: 25 Feb 2023
  • alpha2-adrenoreceptor agonist
  • absence epilepsy
  • genetic rat model
  • Dexdomitor
Video Introduction

This video is adapted from 10.3390/ijms24021477

Electroencephalography (EEG) is widely used to examine electrical brain activity in clinical practise and in basic research.

High voltage spike-wave discharges (SWDs) in EEG are the hallmark of idiopathic generalized epilepsy in humans [1][2][3][4][5]; and the same pathology has been found in some inbred rats, such as WAG/Rij and GAERS rats [6][7][8][9][10].

SWDs in rats usually occur during passive wakefulness, behavioral immobility, drowsiness and light slow-wave sleep (i.e.,  [7][10][11]).

This video demonstrates SWDs in an 8-months old female WAG/Rij. EEG in this rat was recorded with 3 epidural electrodes implanted over the frontal cortex (left and right) and over the occipital cortex. Video-EEG recording was performed free behavior using ADinstruments PowerLab 7.0. The first spontaneous SWD appeared during passive wakefulness and the second SWD - during  slow-wave sleep.

Next, the rat was injected with the synthetic alpha2-adrenoreceptor agonist (i.p. Dexmedetomidine, 0.05mg/kg). This drug has sedative and analgesic properties and is widely used in veterinary practise as Dexdomitor. Two minutes after the injection (prior to the phase of deep sedation) SWDs appeared to interrupt active behavior that is not typical for rats.

As far as the rat recovered from the deep sedation (4 hours 37 min after injection), SWDs again appeared during active behavior.

Agonists of alpha2-adrenoreceptors did not provoke spike-wave seizures in non-epileptic rats. 

Taken together with the concept introduced in their review, researchers conclude that alpha-adrenergic drugs have dual effects: they cause sedation and promote spike-wave activity. Further studies are required to understand the functional link between sedation and spike-wave activity under common control of brain alpha-adrenoreceptor mechanisms.        

The study protocol was approved by the Ethics Committee of Institute of the Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences (protocol No. 4 approved on 26 October 2021). The entry was performed with financial support of RSF (grant number 23-25-00166).

References
  1. Seneviratne, U.; Cook, M.; D’Souza, W. The Electroencephalogram of Idiopathic Generalized Epilepsy. Epilepsia 2012, 53, 234–248.
  2. Lüders, H.; Acharya, J.; Baumgartner, C.; Benbadis, S.; Bleasel, A.; Burgess, R.; Dinner, D.S.; Ebner, A.; Foldvary, N.; Geller, E.; et al. A New Epileptic Seizure Classification Based Exclusively on Ictal Semiology. Acta Neurol. Scand. 1999, 99, 137–141.
  3. ILAE Proposal for Revised Classification of Epilepsies and Epileptic Syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1989, 30, 389–399.
  4. Sadleir, L.G.; Scheffer, I.E.; Smith, S.; Carstensen, B.; Farrell, K.; Connolly, M.B. EEG Features of Absence Seizures in Idiopathic Generalized Epilepsy: Impact of Syndrome, Age, and State. Epilepsia 2009, 50, 1572–1578.
  5. Hirsch, E.; French, J.; Scheffer, I.E.; Bogacz, A.; Alsaadi, T.; Sperling, M.R.; Abdulla, F.; Zuberi, S.M.; Trinka, E.; Specchio, N.; et al. ILAE Definition of the Idiopathic Generalized Epilepsy Syndromes: Position Statement by the ILAE Task Force on Nosology and Definitions. Epilepsia 2022, 63, 1475–1499.
  6. Depaulis, A.; Charpier, S. Pathophysiology of Absence Epilepsy: Insights from Genetic Models. Neurosci. Lett. 2018, 667, 53–65.
  7. Depaulis, A.; Luijtellar, G. van Genetic Models of Absence Epilepsy in the Rat. In Models of Seizures and Epilepsy; Elsevier Inc.: Amsterdam, The Netherlands, 2006; pp. 233–248. ISBN 9780120885541.
  8. Russo, E.; Citraro, R.; Constanti, A.; Leo, A.; Lüttjohann, A.; van Luijtelaar, G.; De Sarro, G. Upholding WAG/Rij Rats as a Model of Absence Epileptogenesis: Hidden Mechanisms and a New Theory on Seizure Development. Neurosci. Biobehav. Rev. 2016, 71, 388–408.
  9. Bazyan, A.S.; van Luijtelaar, G. Neurochemical and Behavioral Features in Genetic Absence Epilepsy and in Acutely Induced Absence Seizures. ISRN Neurol. 2013, 2013, 1–48.
  10. Coenen, A.M.L.; Van Luijtelaar, E.L.J.M. Genetic Animal Models for Absence Epilepsy: A Review of the WAG/Rij Strain of Rats. Behav. Genet. 2003, 33, 635–655.
  11. Riekkinen, P.; Sirviö, J.; Jäkälä, P.; Lammintausta, R.; Riekkinen, P. Interaction between the Alpha 2-Noradrenergic and Muscarinic Systems in the Regulation of Neocortical High Voltage Spindles. Brain Res. Bull. 1990, 25, 147–149.
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Sitnikova, E. Spike-Wave Seizures in WAG/Rij Rat: Baseline and Dexmedetomidine. Encyclopedia. Available online: https://encyclopedia.pub/video/video_detail/628 (accessed on 23 February 2024).
Sitnikova E. Spike-Wave Seizures in WAG/Rij Rat: Baseline and Dexmedetomidine. Encyclopedia. Available at: https://encyclopedia.pub/video/video_detail/628. Accessed February 23, 2024.
Sitnikova, Evgenia. "Spike-Wave Seizures in WAG/Rij Rat: Baseline and Dexmedetomidine" Encyclopedia, https://encyclopedia.pub/video/video_detail/628 (accessed February 23, 2024).
Sitnikova, E. (2023, February 25). Spike-Wave Seizures in WAG/Rij Rat: Baseline and Dexmedetomidine. In Encyclopedia. https://encyclopedia.pub/video/video_detail/628
Sitnikova, Evgenia. "Spike-Wave Seizures in WAG/Rij Rat: Baseline and Dexmedetomidine." Encyclopedia. Web. 25 February, 2023.