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Voluntary physical activity and pharmacological treatment with the Ginkgo biloba extract EGb 761 alleviate regional alterations in cerebral synaptic density and improve behavioral recovery after unilateral labyrinthectomy in the rat

Year: 2026

Type: article

Abstract: Background Unilateral peripheral vestibular loss induces adaptive mechanisms of cerebral plasticity. The quantified Ginkgo biloba extract EGb 761 ® has been shown to enhance neural plasticity, and is used in the treatment of vertigo and dizziness. We here aimed to investigate, how voluntary physical training in a running wheel (RWT) and oral treatment with EGb 761 ® affect behavioral recovery and whole-brain synaptic density following chemical unilateral labyrinthectomy (cUL) in the rat. Methods Thirty-two Sprague Dawley rats were divided into 4 groups with different treatment regimens (group 1: control food; group 2: control food + RWT; group 3: EGb 761 ® food (75mg/day/kg body weight); group 4: EGb 761 ® food + RWT). All rats underwent a left-sided cUL by transtympanic injection of bupivacaine and p-arsanilic acid. Behavioral testing (scoring of nystagmus, postural asymmetry, head tilt, locomotion tracking in open field) was done weekly until 9 weeks (d63) after cUL. Serial [ 18 F]UCB-H μPET imaging of synaptic density (targeting synaptic vesicular protein 2A) was performed before and up to 9 weeks post cUL. Images were whole-brain normalized and segmented based on Schiffer's atlas. Voxel-wise and regional changes of cerebral [ 18 F]UCB-H uptake were compared across groups and time points. Results All rats showed signs of acute vestibular syndrome following cUL. The EGb 761 ® + RWT group had a significantly faster and more complete improvement of postural asymmetry by week 5 post UL and a higher locomotor velocity thereafter than the control food group. Compared to baseline, at d63 post cUL the EGb 761 ® group showed the smalles reduction of synaptic density in the vestibular nuclei of−7.59 ± 7.0 % (vs.−20.37 ± 5.18% in control food group, p < 0.001). In contrast, at d63 post cUL the motor cortex displayed the highest relative gain of synaptic density in the control food group (6.6 ± 3.13 % vs. 0.19 ± 2.81% in the EGb 761 ® group, p < 0.001). All treatment groups showed an increase of synaptic density in the hippocampal area and the somatosensory cortex at weeks 1-3 post cUL compared to the control food group. The additive effect of EGb 761 ® and RWT was statistically confirmed in behavior and PET measurements. Conclusions Unilateral labyrinthectomy induces loss of synaptic density in vestibulo-cerebellar networks, which can be partially reversed by EGb 761 ® treatment. Combined physical and EGb 761 ® treatment improves behavioral recovery from cUL most effectively, reinforcing the importance of multimodal treatment in acute vestibulopathies.

Source: Frontiers in Neurology

DOI: 10.3389/fneur.2026.1937612