Ginkgo biloba Extract EGb 761 Improves Vestibular Compensation and Modulates Cerebral Vestibular Networks in the Rat.
Front Neurol. 2019 Feb 25;10:147. doi: 10.3389/fneur.2019.00147. eCollection 2019.
|Authors/Editors:||Lindner M, Gosewisch A, Eilles E, Branner C, Krämer A, Oos R, Wolf E, Ziegler S, Bartenstein P, Brandt T, Dieterich M, Zwergal A.|
Unilateral inner ear damage is followed by behavioral recovery due to central vestibularcompensation. The dose-dependent therapeutic effect ofGinkgo bilobaextract EGb 761on vestibular compensation was investigated by behavioraltesting and serial cerebral[18F]-Fluoro-desoxyglucose ([18F]-FDG)-μPET in a rat model of unilateral labyrinthectomy(UL). Five groups of 8 animals each were treated with EGb 761-supplemented food atdoses of 75, 37.5 or 18.75 mg/kg body weight 6 weeks prior and 15 days post UL(groups A,B,C), control food prior and EGb 761-supplemented food (75 mg/kg) for 15days post UL (group D), or control food throughout (group E).Plasma levels of EGb 761components bilobalide, ginkgolide A and B were analyzed prior and 15 days post UL.Behavioral testing included clinical scoring of nystagmus, postural asymmetry, head rolltilt, body rotation during sensory perturbation and instrumental registration of mobility inan open field before and 1, 2, 3, 5, 7, 15 days after UL. Whole-brain [18F]-FDG-μPETwas recorded before and 1, 3, 7, 15 days after UL. The EGb 761 group A (75 mg/kgprior/post UL) showed a significant reduction of nystagmus scores (day 3 post UL),of postural asymmetry (1, 3, 7 days post UL), and an increasedmobility in the openfield (day 7 post UL) as compared to controls (group E). Application of EGb 761 atdoses of 37.5 and 18.75 mg/kg prior/post UL (groups B,C) resulted in faster recoveryof postural asymmetry, but did not influence mobility relative to controls. Locomotorvelocity increased with higher plasma levels of ginkgolideA and B. [18F]-FDG-μPETrevealed a significant decrease of the regional cerebral glucose metabolism (rCGM) inthe vestibular nuclei and cerebellum and an increase in the hippocampal formation withhigher plasma levels of ginkgolides and bilobalide 1 and 3 days post UL. Decrease ofrCGM in the vestibular nucleus area and increase in the hippocampal formation withhigher plasma levels persisted until day 15 post UL. In conclusion,Ginkgo bilobaextractEGb 761 improves vestibulo-ocular motor, vestibulo-spinal compensation, and mobilityafter UL. This rat study supports the translational approach to investigate EGb 761 athigher dosages for acceleration of vestibular compensation in acute vestibular loss.