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Neurotoxicity Research

, Volume 33, Issue 4, pp 837–845 | Cite as

The Antiepileptic Drug Levetiracetam Protects Against Quinolinic Acid-Induced Toxicity in the Rat Striatum

  • Maricela Dircio-Bautista
  • Ana Laura Colín-González
  • Gabriela Aguilera
  • Marisol Maya-López
  • Juana Villeda-Hernández
  • Sonia Galván-Arzate
  • Esperanza García
  • Isaac Túnez
  • Abel Santamaría
ORIGINAL ARTICLE

Abstract

Levetiracetam (LVT) is a relatively novel antiepileptic drug (AED) known to act through binding with the synaptic vesicular 2A (SV2A) protein, thus modulating the presynaptic neurotransmitter release. The tryptophan metabolite quinolinic acid (QUIN) acts as an excitotoxin when its brain concentrations reach toxic levels under pathological conditions. Since increased neuronal excitability induced by QUIN recruits degenerative events in the brain, and novel AED is also expected to exert neuroprotective effects in their pharmacological profiles, in this work the effect of LVT (54 mg/kg, i.p., administered for seven consecutive days) was tested as a pretreatment against the toxicity evoked by the bilateral intrastriatal injection of QUIN (60 nmol/μl) to adult rats. QUIN increased the striatal levels of peroxidized lipids and carbonylated proteins as indexes of oxidative damage 24 h after its infusion. In addition, in synaptosomal fractions isolated from QUIN-lesioned rats 24 h after the toxin infusion, γ-aminobutyric acid (GABA) release was decreased, whereas glutamate (Glu) release was increased. QUIN also decreased motor activity and augmented the rate of cell damage at 7 days post-lesion. All these alterations were significantly prevented by pretreatment of rats with LVT. The results of this study show a neuroprotective role and antioxidant action of LVT against the brain damage induced by excitotoxic events.

Keywords

Excitotoxicity Neurotransmitter release Oxidative damage Motor alterations Brain tissue damage Antiepileptic drug 

Notes

Compliance with Ethical Standards

The experimental protocols were approved by the Ethics Committee of the INNN.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Maricela Dircio-Bautista
    • 1
    • 2
  • Ana Laura Colín-González
    • 1
  • Gabriela Aguilera
    • 1
  • Marisol Maya-López
    • 1
  • Juana Villeda-Hernández
    • 3
  • Sonia Galván-Arzate
    • 4
  • Esperanza García
    • 5
  • Isaac Túnez
    • 6
  • Abel Santamaría
    • 1
  1. 1.Laboratorio de Aminoácidos ExcitadoresInstituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A.Mexico CityMexico
  2. 2.Facultad de CienciasUniversidad Nacional Autónoma de MéxicoMexico CityMexico
  3. 3.Laboratorio de Patología ExperimentalInstituto Nacional de Neurología y Neurocirugía, S.S.A.Mexico CityMexico
  4. 4.Departamento de NeuroquímicaInstituto Nacional de Neurología y Neurocirugía, S.S.A.Mexico CityMexico
  5. 5.Laboratorio de NeuroinmunologíaInstituto Nacional de Neurología y Neurocirugía, S.S.A.Mexico CityMexico
  6. 6.Departamento de Bioquímica y Biología Molecular, Facultad de Medicina y Enfermería, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)Universidad de CórdobaCordobaSpain

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