Sodium Valproate Reduces Neuronal Apoptosis in Acute Pentylenetetrzole-Induced Seizures via Inhibiting ER Stress

  • Jie Fu
  • Lilei Peng
  • Weijun Wang
  • Haiping He
  • Shan Zeng
  • Thomas C. ChenEmail author
  • Yangmei ChenEmail author
Original Paper


Endoplasmic reticulum (ER) stress has been indicated to be involved in the pathogenesis of epilepsy. Sodium valproate (VPA), one of the most commonly used antiepileptic drugs, is reported to regulate ER stress in many neurological diseases. However, the effect of VPA on ER stress in epilepsy remains unclear. The current study was performed to investigate the role of ER stress in the neuroprotection of VPA against seizure induced by pentylenetetrzole (PTZ). Our results showed that VPA treatment could inhibit the increased expressions of ER stress proteins (GRP78 and CHOP), and significantly reduce neuronal apoptosis in the PTZ-induced experimental seizure model. In addition, Salubrinal, an ER stress inhibitor, was used as a positive control, and exhibited neuroprotective effects via inhibiting excessive ER stress in the seizure model, which further supported that the inhibition in ER stress by VPA treatment could exert neuroprotection in seizures. In summary, our work demonstrated for the first time that ER stress was involved in the neuroprotective potential of VPA for seizures.


Sodium valproate ER stress Neuronal apoptosis Pentylenetetrazole Epilepsy 


Compliance with Ethical Standards

Conflict of interest

We declared no potential conflict of interest.


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

Authors and Affiliations

  1. 1.Department of NeurologyThe Second Affiliated Hospital of Chongqing Medical UniversityChongqingChina
  2. 2.Department of NeurologyThe Affiliated Hospital of Southwest Medical UniversityLuzhouChina
  3. 3.Department of NeurosurgeryThe Affiliated Hospital of Southwest Medical UniversityLuzhouChina
  4. 4.Departments of Neurological Surgery, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

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