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Combination Therapy of Gabapentin and N-Acetylcysteine Against Posttraumatic Epilepsy in Rats

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Abstract

Traumatic brain injury (TBI) is a major public health problem worldwide that is associated with increased mortality and morbidity. Posttraumatic epilepsy (PTE) is one of the sequelae of TBI. The aim of this study was to investigate the role of N-acetylcysteine (NAC) as an adjuvant on the efficacy of levetiracetam (LEV) and gabapentin (GBP) in PTE model encouraged by pentylenetetrazol (PTZ) after mild-TBI in male Sprague–Dawley rats. Mild-TBI was performed by the weight-drop method in male Sprague–Dawley rats. PTE model was developed by injecting PTZ (30+15+15 mg/kg, 30 min intervals, i.p.) 7 days after head trauma. After the development of posttraumatic seizures, the rats were treated with NAC (100 mg/kg), LEV (50 mg/kg), GBP (100 mg/kg), NAC+LEV and NAC+GBP intraperitoneally for 14 days. Seizures related to PTE were scored by video-EEG recording. Motor performance of the animals was also evaluated in the rotarod test. 50 mg/kg LEV and 100 mg/kg GBP reduced seizures related to PTE. LEV alone (p = 0.009), but the administration of GBP+NAC (p = 0.015) was more effective on PTE-related seizure control. However, GBP+NAC application adversely affected the fall latency in the rotarod test. In terms of trauma-related seizure control, there was no statistically significant difference between the use of prophylactic LEV and symptomatic LEV. LEV alone or the combination of GBP with NAC provides more effective seizure control in the PTE facilitated by PTZ. On the other hand, the use of prophylactic LEV did not have any extra effect on posttraumatic seizure development and control.

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Abbreviations

AED:

Antiepileptic drug

GBP:

Gabapentin

LEV:

Levetiracetam

NAC:

N-Acetylcysteine

PHT:

Phenytoin

PTE:

Posttraumatic epilepsy

PTZ:

Pentylenetetrazol

TBI:

Traumatic brain injury

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Authors and Affiliations

  1. Department of Neurosurgery, Haydarpaşa Numune Training and Research Hospital, Istanbul, Turkey

    Mustafa Efendioglu

  2. Department of Neurosurgery, Sancaktepe Training and Research Hospital, Istanbul, Turkey

    Recep Basaran & Duygu Ceman

  3. Department of Physiology, Hamidiye Faculty of Medicine, University of Health Sciences, Istanbul, Turkey

    Metehan Akca, Cumaali Demirtas & Mehmet Yildirim

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  1. Mustafa Efendioglu
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  2. Recep Basaran
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Contributions

MY designed the study, performed experiments, analyzed data and the manuscript. ME and RB designed the study, performed experiments and, edited and revised the manuscript. DC designed the study and performed experiments. MA and CD performed experiments and analyzed data. All authors reviewed the content and approved the final version of the manuscript.

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Correspondence to Mehmet Yildirim.

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Efendioglu, M., Basaran, R., Akca, M. et al. Combination Therapy of Gabapentin and N-Acetylcysteine Against Posttraumatic Epilepsy in Rats. Neurochem Res 45, 1802–1812 (2020). https://doi.org/10.1007/s11064-020-03042-x

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  • DOI: https://doi.org/10.1007/s11064-020-03042-x

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