In Vivo Imaging of Glial Activation after Unilateral Labyrinthectomy in the Rat: A [18F]GE180-PET Study

Zwergal, Andreas; Gunther, Lisa M.; Brendel, Matthias; Beck, Roswitha; Lindner, Simon; Xiong, Guoming; Eilles, Eva; Albert, Nathalie L.; Becker‐Bense, Sandra; Brandt, Thomas; Ziegler, Sibylle; Fougère, Christian la; Dieterich, Marianne; Bartenstein, Peter

doi:10.3389/fneur.2017.00665

Cited by 14 publications

(12 citation statements)

References 43 publications

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“…A significant increase in the number of microglial cells was observed three days after UVN persisting up to 30 days post-lesion [9][10][11]. Other groups report the same observation: strong microglial reactions were also observed in the rat deafferented VNs after unilateral labyrinthectomy (UL) [55,56]. The microglial reaction would promote the plasticity mechanisms in the deafferented vestibular environment and, in particular, the level of excitability, which is crucial for functional recovery.…”

Section: Neurobiological Correlates Of Sensorimotor Rehabilitation In the Vnmentioning

confidence: 74%

Sensorimotor Rehabilitation Promotes Vestibular Compensation in a Rodent Model of Acute Peripheral Vestibulopathy by Promoting Microgliogenesis in the Deafferented Vestibular Nuclei

Marouane

Mahmoudi

Rastoldo

et al. 2021

Cells

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Acute peripheral vestibulopathy leads to a cascade of symptoms involving balance and gait disorders that are particularly disabling for vestibular patients. Vestibular rehabilitation protocols have proven to be effective in improving vestibular compensation in clinical practice. Yet, the underlying neurobiological correlates remain unknown. The aim of this study was to highlight the behavioural and cellular consequences of a vestibular rehabilitation protocol adapted to a rat model of unilateral vestibular neurectomy. We developed a progressive sensory-motor rehabilitation task, and the behavioural consequences were quantified using a weight-distribution device. This analysis method provides a precise and ecological analysis of posturolocomotor vestibular deficits. At the cellular level, we focused on the analysis of plasticity mechanisms expressed in the vestibular nuclei. The results obtained show that vestibular rehabilitation induces a faster recovery of posturolocomotor deficits during vestibular compensation associated with a decrease in neurogenesis and an increase in microgliogenesis in the deafferented medial vestibular nucleus. This study reveals for the first time a part of the underlying adaptative neuroplasticity mechanisms of vestibular rehabilitation. These original data incite further investigation of the impact of rehabilitation on animal models of vestibulopathy. This new line of research should improve the management of vestibular patients.

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Section: Neurobiological Correlates Of Sensorimotor Rehabilitation In the Vnmentioning

confidence: 74%

Sensorimotor Rehabilitation Promotes Vestibular Compensation in a Rodent Model of Acute Peripheral Vestibulopathy by Promoting Microgliogenesis in the Deafferented Vestibular Nuclei

Marouane

Mahmoudi

Rastoldo

et al. 2021

Cells

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“…In contrast, due to its baseline dependency, the longitudinal decrease of the Z -score difference towards late ages is a rather compelling readout unlikely to be biased by possible tracer sensitivity differences. Furthermore, ceiling effects are unlikely as far higher magnitudes of TSPO activation and amyloidosis can be detected with these tracers in other circumstances [ 31 , 40 ]. Thus, our serial dual tracer μPET imaging proves that microglial activation saturates during an ongoing fibrillar amyloid deposition in this mouse model (Figs.…”

Section: Discussionmentioning

confidence: 99%

Microglial response to increasing amyloid load saturates with aging: a longitudinal dual tracer in vivo μPET-study

Blume

Focke

Peters

et al. 2018

J Neuroinflammation

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BackgroundCausal associations between microglia activation and β-amyloid (Aβ) accumulation during the progression of Alzheimer’s disease (AD) remain a matter of controversy. Therefore, we used longitudinal dual tracer in vivo small animal positron emission tomography (μPET) imaging to resolve the progression of the association between Aβ deposition and microglial responses during aging of an Aβ mouse model.MethodsAPP-SL70 mice (N = 17; baseline age 3.2–8.5 months) and age-matched C57Bl/6 controls (wildtype (wt)) were investigated longitudinally for 6 months using Aβ (18F-florbetaben) and 18 kDa translocator protein (TSPO) μPET (18F-GE180). Changes in cortical binding were transformed to Z-scores relative to wt mice, and microglial activation relative to amyloidosis was defined as the Z-score difference (TSPO—Aβ). Using 3D immunohistochemistry for activated microglia (Iba-1) and histology for fibrillary Aβ (methoxy-X04), we measure microglial brain fraction relative to plaque size and the distance from plaque margins.ResultsAβ-PET binding increased exponentially as a function of age in APP-SL70 mice, whereas TSPO binding had an inverse U-shape growth function. Longitudinal Z-score differences declined with aging, suggesting that microglial response declined relative to increasing amyloidosis in aging APP-SL70 mice. Microglial brain volume fraction was inversely related to adjacent plaque size, while the proximity to Aβ plaques increased with age.ConclusionsMicroglial activity decreases relative to ongoing amyloidosis with aging in APP-SL70 mice. The plaque-associated microglial brain fraction saturated and correlated negatively with increasing plaque size with aging.

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“…Most important regions for reorganization are the vestibular nuclei, the vestibulocerebellum, the thalamus and hippocampus (3–7). Mechanisms of VC can be examined on a cellular and neuronal level by various histological and electrophysiological techniques or on a whole brain network level using in vivo methods like serial positron emission tomography (PET) (8–10). Characteristic changes of regional cerebral glucose metabolism (rCGM) have been depicted recently after unilateral labyrintectomy (UL) in the rat using [ 18 F]-Fluoro-desoxyglucose ([ 18 F]-FDG)-μPET (9).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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In Vivo Imaging of Glial Activation after Unilateral Labyrinthectomy in the Rat: A [18F]GE180-PET Study

Cited by 14 publications

References 43 publications

Sensorimotor Rehabilitation Promotes Vestibular Compensation in a Rodent Model of Acute Peripheral Vestibulopathy by Promoting Microgliogenesis in the Deafferented Vestibular Nuclei

Sensorimotor Rehabilitation Promotes Vestibular Compensation in a Rodent Model of Acute Peripheral Vestibulopathy by Promoting Microgliogenesis in the Deafferented Vestibular Nuclei

Microglial response to increasing amyloid load saturates with aging: a longitudinal dual tracer in vivo μPET-study

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

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