Investigating the mechanism of action of ginkgolides and bilobalide on absence seizures in male WAG/Rij rats.


Gedikli Ö., Akca M., Yildirim M.

Journal of neuroscience research, vol.101, no.6, pp.866-880, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 101 Issue: 6
  • Publication Date: 2023
  • Doi Number: 10.1002/jnr.25166
  • Journal Name: Journal of neuroscience research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Animal Behavior Abstracts, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.866-880
  • Keywords: bilobalide, Ginkgo biloba, ginkgolides, spike-wave discharges, WAG, Rij rat, SPIKE-WAVE DISCHARGES, GENETIC ANIMAL-MODELS, RECEPTOR ANTAGONISTS, EPILEPTIC ACTIVITY, CALCIUM-CHANNELS, MK-801, AMPA, EXTRACT, STRAIN, INVOLVEMENT
  • Karadeniz Technical University Affiliated: Yes

Abstract

The effects of a single and multiple doses of ginkgolide A, B, C, and bilobalide, active components of Ginkgo biloba extract (EGb 761), on absence seizures were investigated in male WAG/Rij rats, a genetic animal model of absence epilepsy. Furthermore, the interactions of ginkgolide A together with NMDA receptor antagonist MK-801, AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), or L-type calcium channel blocker nicardipine were studied to figure out how ginkgolide A affects spike-wave discharges (SWDs) in the brain. The experiments were done using 6-8-month-old male WAG/Rij rats with infusion cannula and EEG electrode implanted. Ginkgolide A, B, C, and bilobalide were administered intraperitoneally for 7 days at a dose of 6 mg/kg. In interaction groups, 6 mu g ginkgolide A was injected intracerebroventricularly in combination with MK-801 (10 mu g), CNQX (1 mu g), and nicardipine (50 mu g) for 7 days. EEG was recorded from animals at the baseline, first dose, and seventh dose periods for 4 h. Ginkgolide A (p = .028), C (p = .046), and bilobalide (p = .043) significantly increased the frequency of SWDs in WAG/Rij rats. Ginkgolide A injected into the lateral ventricle with MK-801 (p = .046), CNQX (p = .043), and nicardipine (p = .046) significantly increased the number of SWDs after seventh dose. Finally, the EGb 761-related increase in absence epilepsy was determined to be caused by ginkgolide A, C, and bilobalide. All three receptor antagonists/channel blockers do not inhibit the pro-absence effect of ginkgolide A. The findings revealed that ginkgolide A's pro-absence effect is mediated by brain circuits other than ionotropic glutamate receptors or L-type calcium channels.