Ginkgo biloba Extract EGb 761 Improves Vestibular Compensation and Modulates Cerebral Vestibular Networks in the Rat

Abstract

Unilateral inner ear damage is followed by behavioral recovery due to central vestibular compensation. The dose-dependent therapeutic effect of Ginkgo biloba extract EGb 761 on vestibular compensation was investigated by behavioral testing and serial cerebral [ 18 F]-Fluoro-desoxyglucose ([ 18 F]-FDG)-μPET in a rat model of unilateral labyrinthectomy (UL). Five groups of 8 animals each were treated with EGb 761-supplemented food at doses 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 15 days post UL (group D), or control food throughout (group E). Plasma levels of EGb 761 components bilobalide, ginkgolide A and B were analyzed prior and 15 days post UL. Behavioral testing included clinical scoring of nystagmus, postural asymmetry, head roll tilt, body rotation during sensory perturbation and instrumental registration of mobility in an open field before and 1, 2, 3, 5, 7, 15 days after UL. Whole-brain [ 18 F]-FDG-μPET was recorded before and 1, 3, 7, 15 days after UL. The EGb 761 group A (75 mg/kg prior/post UL) showed a significant reduction of nystagmus scores (day 3 post UL), of postural asymmetry (1, 3, 7 days post UL), and an increased mobility in the open field (day 7 post UL) as compared to controls (group E). Application of EGb 761 at doses of 37.5 and 18.75 mg/kg prior/post UL (groups B,C) resulted in faster recovery of postural asymmetry, but did not influence mobility relative to controls. Locomotor velocity increased with higher plasma levels of ginkgolide A and B. [ 18 F]-FDG-μPET revealed a significant decrease of the regional cerebral glucose metabolism (rCGM) in the vestibular nuclei and cerebellum and an increase in the hippocampal formation with higher plasma levels of ginkgolides and bilobalide 1 and 3 days post UL. Decrease of rCGM in the vestibular nucleus area and increase in the hippocampal formation with higher plasma levels persisted until day 15 post UL. In conclusion, Ginkgo biloba extract EGb 761 improves vestibulo-ocular motor, vestibulo-spinal compensation, and mobility after UL. This rat study supports the translational approach to investigate EGb 761 at higher dosages for acceleration of vestibular compensation in acute vestibular loss.

Quantitative Evaluation of a New Posturo-Locomotor Phenotype in a Rodent Model of Acute Unilateral Vestibulopathy

“…Certain parameters, such as velocity, were compensated within 7 days post-UVN. These results corroborate those of Lindner et al (29) in a chemical model of unilateral labyrinthectomy. In this model, rats demonstrated a significant increase in their velocity above baseline after day 7.…”

“…In most cases, walking balance tests are not useful for screening people for vestibular impairments but can be useful in vestibular rehabilitation in patients with known diagnoses (24). Among the large number of studies that have investigated postural and ocular reflex deficits after acute unilateral vestibular loss in rats, only a few have thoroughly investigated locomotor activity (27)(28)(29) (Porter et al, 1990). Furthermore, the analysis is restricted to velocity, distance traveled, or spatial exploration behavior.…”

Breaking a Dogma: Acute Anti-Inflammatory Treatment Alters Both Post-Lesional Functional Recovery and Endogenous Adaptive Plasticity Mechanisms in a Rodent Model of Acute Peripheral Vestibulopathy.

“…Locomotor activity in rats after UVN was quantified in an automated and unbiased manner under ecological conditions, through the use of different quantitative parameters, recently validated as part of a specific posturo-locomotor phenotype after UVN (Rastoldo et al, 2020). In accordance with previous works, we observed a significant increase of these parameters with time, confirming the persistent hyperactivity after vestibular loss (Lindner et al, 2019;Rastoldo et al, 2020). This could represent a compensatory strategy since by increasing locomotion velocity, automatic spinal networks inhibit misleading vestibular information (Fabre-Adinolfi et al, 2018).…”

A New and Faster Method to Assess Vestibular Compensation: A Cross‐Sectional Study

“…3,4 In experimental animals, the static component of the vestibular syndrome is evaluated and its follow-up easily tracked measuring the frequency (or slow-phase velocity [SPV]) of spontaneous nystagmus until its disappearance, and the degree of head tilt until its normalization. 5 Compensation of that early component occurs when equivalent activity between the ipsilesional and contralesional vestibular nuclei is restored after several levels of modulation. 6 The dynamic component of the vestibular syndrome is usually the main problem during the most challenging situations and has a high impact on the patient's daily activities.…”