Longitudinal comparison of adaptive neuroplasticity in two rat models of unilateral vestibulopathy by dual-tracer [18F]FDG and [18F]UCB-H PET

Animal models of acute unilateral vestibulopathy are well established for the study of adaptive lesion-induced neuroplasticity, because symptoms of acute vestibular asymmetry such as nystagmus and postural imbalance recover over time as central vestibular compensation mechanisms commence action. The purpose of this study was to compare these mechanisms in a postganglionic complete unilateral vestibular neurectomy model (UVN) vs. a preganglionic incomplete chemical unilateral labyrinthectomy model (cUL) using a longitudinal [¹⁸F]FDG/[¹⁸F]UCB-H dual tracer positron emission tomography (PET) approach accompanied by multimodal behavioral testing. Twenty-four male Sprague Dawley rats underwent either cUL or UVN. Postoperatively, [¹⁸F]FDG PETs were conducted weekly for four weeks to depict changes of [¹⁸F]FDG as a surrogate for functional plasticity, and [¹⁸F]UCB-H PETs were carried out at three time points over nine weeks to visualize alterations in synaptic density indicating structural plasticity. Behavioral recovery was assessed weekly using a clinical scoring system and open field evaluation. Behavioral data reflected comparable compensation dynamics between groups. Both [¹⁸F]FDG and [¹⁸F]UCB-H PET revealed a similar spatial pattern of brain regions involved in adaptive neuroplasticity. However, while the relative extent of [¹⁸F]FDG uptake in these networks was comparable across both models, synaptic density changes were more pronounced in UVN vs. cUL. Specifically, synaptic density in the vestibular nuclei was significantly lower after UVN, accompanied by a more intense compensatory increase in sensorimotor cortical areas. In conclusion, synaptic density imaging may be a more sensitive method to depict subtle differences in mechanisms of lesion-induced adaptive neuroplasticity than traditional techniques such as imaging of glucose metabolism.