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The Possible Role of Nitric Oxide Pathway in Pentylenetetrazole Preconditioning Against Seizure in Mice

  • Hedyeh Faghir-Ghanesefat
  • Hedieh Keshavarz-Bahaghighat
  • Nazanin Rajai
  • Tahmineh Mokhtari
  • Erfan Bahramnejad
  • Soheil Kazemi Roodsari
  • Ahmad Reza DehpourEmail author
Article
  • 13 Downloads

Abstract

Preconditioning is defined as an induction of adaptive response in organs against lethal stimulation provoked by subsequent mild sublethal stress. Several chemical agents have been demonstrated to cause brain tolerance through preconditioning. The aim of the present study is to test the hypothesis that preconditioning with pentylenetetrazole (PTZ) may have protective effect against seizure induced by i.v. infusion of PTZ. Mice were preconditioned by low-dose administration of PTZ (25 mg/kg) for 5 consecutive days, and the threshold of seizure elicited by i.v. infusion of PTZ was measured. To investigate the possible role of nitric oxide, NOS inhibitor enzymes, including L-NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) (10 mg/kg), aminoguanidine (AG) (50 mg/kg), 7-nitroindazole (7-NI) (15 mg/kg), and L-arginine (L-arg) (60 mg/kg), were administered concomitantly with PTZ in both acute and chronic phases. Determination of seizure threshold revealed significant enhancement after preconditioning with low dose of PTZ. While the protective effect of PTZ preconditioning was enhanced after the administration of L-arg, it was reversed following administration of L-NAME and 7NI, suggesting the involvement of nitric oxide pathway as an underlying mechanism of PTZ-induced preconditioning. Preconditioning with PTZ led to brain tolerance and adaptive response in animal model of PTZ-induced seizure. This effect is in part due to the involvement of nitric oxide pathway.

Keywords

Pentylenetetrazole Preconditioning Nitric oxide Seizure Mice 

Notes

Funding Statement

This study was funded and supported by Experimental Medicine Research Center, Tehran University of Medical Sciences (http://tums.ac.ir/?lang=en), grant no. 97-01-158-37318 to AD, and a grant (96002757) from Iran National Science Foundation (INSF).

Compliance with Ethical Standards

All applicable international and institutional guidelines for the care and use of animals were followed.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hedyeh Faghir-Ghanesefat
    • 1
    • 2
  • Hedieh Keshavarz-Bahaghighat
    • 1
    • 2
  • Nazanin Rajai
    • 1
    • 2
  • Tahmineh Mokhtari
    • 3
    • 4
  • Erfan Bahramnejad
    • 1
    • 2
  • Soheil Kazemi Roodsari
    • 1
    • 2
  • Ahmad Reza Dehpour
    • 1
    • 2
    Email author
  1. 1.Department of Pharmacology, School of MedicineTehran University of Medical SciencesTehranIran
  2. 2.Experimental Medicine Research CenterTehran University of Medical SciencesTehranIran
  3. 3.Nervous System Stem Cells Research CenterSemnan University of Medical SciencesSemnanIran
  4. 4.Department of Anatomy, School of MedicineSemnan University of Medical SciencesSemnanIran

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