Research Article

Unaltered trace element levels following the absence status induction by an alpha 2A receptor agonist in the cortex and hippocampus of genetic absence epilepsy rats

Volume: 29 Number: 2 April 8, 2025
  • Melis Yavuz *
  • Gokcen Dolu
  • Rui Azevedo
  • Agostinho Almeida
  • Filiz Onat
EN

Unaltered trace element levels following the absence status induction by an alpha 2A receptor agonist in the cortex and hippocampus of genetic absence epilepsy rats

Abstract

This study builds upon our prior investigation proposing a potential animal model for absence status epilepticus induced by specific alpha-2a adrenergic receptor (α2AAR) activation through intracerebroventricular injection of dexmedetomidine (DEX). Our objective was to explore trace element levels within the cortex of genetic absence epilepsy rats from Strasbourg (GAERS) during absence status induction through α2AAR activation. Stereotaxic surgery was performed on adult GAERS to implant recording electrodes in the frontoparietal cortices under anesthesia. Following intracerebroventricular injection of the α2AAR agonist, DEX, the electroencephalography (EEG) was recorded. After inducing the second period of absence statuses, the rats were euthanized. Trace elements were analyzed using inductively coupled plasma mass spectrometry (ICP/MS) among the groups: GAERS-NAÏVE, GAERS injected with saline (GAERS-SAL), and GAERS injected with DEX (GAERS-DEX). No significant differences of the levels of trace elements were observed in the GAERS-DEX group compared to GAERS-SAL following absence status induction. Conversely, significant differences in trace element levels were identified between the GAERS-NAÏVE and GAERS-SAL or GAERS-DEX groups. Cortical levels of 25Mg, 55Mn, 57Fe, 88Sr, 65Cu, 42Mo, 80Hg, 15P, 52Cr, 59Co, 66Zn, 82Se, 85Rb, 133Cs, and 205Tl were higher in the GAERS-NAÏVE group compared to GAERS-SAL (p < 0.05). Similarly, hippocampal levels of 25Mg, 43Ca, 55Mn, 57Fe, 88Sr, 65Cu, 42Mo, 80Hg, 15P, 52Cr, 59Co, 66Zn, 82Se, 85Rb, 133Cs, and 205Tl were higher in the GAERS-NAÏVE group compared to the GAERS-SAL group (p < 0.05). Our findings suggest that DEXinduced absence status does not alter trace element levels in the cortex and hippocampus, unlike convulsive forms of epilepsies. However, the influence of trace element modulations on the development of absence status remains open to discussion. Intriguingly, cannula placement appeared to affect trace element levels, prompting inquiries into the current methodology of intracerebroventricular cannula implementation.

Keywords

References

  1. [1] Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshe SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010; 51(6): 1069-1077. https://doi.org/10.1111/j.1528-1167.2009.02397.x.
  2. [2] Trinka E, Hofler J, Leitinger M, Brigo F. Pharmacotherapy for status epilepticus. Drugs. 2015; 75(13): 1499-1521. https://doi.org/10.1007/s40265-015-0454-2
  3. [3] Leitinger M, Trinka E, Giovannini G, Zimmermann G, Florea C, Rohracher A, Kalss G, Neuray C, Kreidenhuber R, Höfler J, Kuchukhidze G, Granbichler C, Dobesberger J, Novak HF, Pilz G, Meletti S, Siebert U. Epidemiology of status epilepticus in adults: A population-based study on incidence, causes, and outcomes. Epilepsia. 2019; 60(1): 53-62. https://doi.org/10.1111/epi.14607
  4. [4] Leitinger M, Beniczky S, Rohracher A, Gardella E, Kalss G, Qerama E, Hofler J, Hess Lindberg-Larsen A, Kuchukhidze G, Dobesberger J, Langthaler PB, Trinka E. Salzburg Consensus criteria for non-convulsive status epilepticus--approach to clinical application. Epilepsy Behav. 2015; 49:158-163. https://doi.org/10.1016/j.yebeh.2015.05.007
  5. [5] Leitinger M, Trinka E, Gardella E, Rohracher A, Kalss G, Qerama E, Hofler J, Hess A, Zimmermann G, Kuchukhidze G, Dobesberger J, Langthaler PB, Beniczky S. Diagnostic accuracy of the Salzburg EEG criteria for non-convulsive status epilepticus: A retrospective study. Lancet Neurol. 2016; 15(10): 1054-1062. https://doi.org/10.1016/S1474-4422(16)30137-5
  6. [6] Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, Shorvon S, Lowenstein DH. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015; 56(10): 1515-1523. https://doi.org/10.1111/epi.13121
  7. [7] Yavuz M, Akkol S, Onat F. Alpha-2a adrenergic receptor (α2AR) activation in genetic absence epilepsy: An absence status model? Epilepsia Open.2024;9(2):534-547. https://doi.org/10.1002/epi4.12879.
  8. [8] Yavuz M, Aydin B, Carcak N, Akman O, Raci Yananli H, Onat F. Atipamezole, a specific alpha2A antagonist, suppresses spike-and-wave discharges and alters Ca(2(+)) /calmodulin-dependent protein kinase II in the thalamus of genetic absence epilepsy rats. Epilepsia. 2020; 61(12):2825-2835. https://doi.org/10.1111/epi.16728

Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences (Other)

Journal Section

Research Article

Authors

Gokcen Dolu This is me
Türkiye

Rui Azevedo This is me
Portugal

Agostinho Almeida This is me
Portugal

Filiz Onat This is me
Türkiye

Publication Date

April 8, 2025

Submission Date

February 2, 2024

Acceptance Date

June 6, 2024

Published in Issue

Year 2025 Volume: 29 Number: 2

APA
Yavuz, M., Dolu, G., Azevedo, R., Almeida, A., & Onat, F. (2025). Unaltered trace element levels following the absence status induction by an alpha 2A receptor agonist in the cortex and hippocampus of genetic absence epilepsy rats. Journal of Research in Pharmacy, 29(2), 590-598. https://doi.org/10.12991/jrespharm.1662084
AMA
1.Yavuz M, Dolu G, Azevedo R, Almeida A, Onat F. Unaltered trace element levels following the absence status induction by an alpha 2A receptor agonist in the cortex and hippocampus of genetic absence epilepsy rats. J. Res. Pharm. 2025;29(2):590-598. doi:10.12991/jrespharm.1662084
Chicago
Yavuz, Melis, Gokcen Dolu, Rui Azevedo, Agostinho Almeida, and Filiz Onat. 2025. “Unaltered Trace Element Levels Following the Absence Status Induction by an Alpha 2A Receptor Agonist in the Cortex and Hippocampus of Genetic Absence Epilepsy Rats”. Journal of Research in Pharmacy 29 (2): 590-98. https://doi.org/10.12991/jrespharm.1662084.
EndNote
Yavuz M, Dolu G, Azevedo R, Almeida A, Onat F (April 1, 2025) Unaltered trace element levels following the absence status induction by an alpha 2A receptor agonist in the cortex and hippocampus of genetic absence epilepsy rats. Journal of Research in Pharmacy 29 2 590–598.
IEEE
[1]M. Yavuz, G. Dolu, R. Azevedo, A. Almeida, and F. Onat, “Unaltered trace element levels following the absence status induction by an alpha 2A receptor agonist in the cortex and hippocampus of genetic absence epilepsy rats”, J. Res. Pharm., vol. 29, no. 2, pp. 590–598, Apr. 2025, doi: 10.12991/jrespharm.1662084.
ISNAD
Yavuz, Melis - Dolu, Gokcen - Azevedo, Rui - Almeida, Agostinho - Onat, Filiz. “Unaltered Trace Element Levels Following the Absence Status Induction by an Alpha 2A Receptor Agonist in the Cortex and Hippocampus of Genetic Absence Epilepsy Rats”. Journal of Research in Pharmacy 29/2 (April 1, 2025): 590-598. https://doi.org/10.12991/jrespharm.1662084.
JAMA
1.Yavuz M, Dolu G, Azevedo R, Almeida A, Onat F. Unaltered trace element levels following the absence status induction by an alpha 2A receptor agonist in the cortex and hippocampus of genetic absence epilepsy rats. J. Res. Pharm. 2025;29:590–598.
MLA
Yavuz, Melis, et al. “Unaltered Trace Element Levels Following the Absence Status Induction by an Alpha 2A Receptor Agonist in the Cortex and Hippocampus of Genetic Absence Epilepsy Rats”. Journal of Research in Pharmacy, vol. 29, no. 2, Apr. 2025, pp. 590-8, doi:10.12991/jrespharm.1662084.
Vancouver
1.Melis Yavuz, Gokcen Dolu, Rui Azevedo, Agostinho Almeida, Filiz Onat. Unaltered trace element levels following the absence status induction by an alpha 2A receptor agonist in the cortex and hippocampus of genetic absence epilepsy rats. J. Res. Pharm. 2025 Apr. 1;29(2):590-8. doi:10.12991/jrespharm.1662084