Secondary thalamic neuroinflammation associates with disturbed corticothalamic connectivity in a model of severe traumatic brain injury in male rats-a longitudinal study.

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. The initial injury initiates a cascade of secondary injury mechanisms, including neuroinflammation and disruption of brain connectivity. In this study, we used the lateral fluid percussion injury model of TBI to investigate the relationship between secondary thalamic inflammation and corticothalamic connectivity disruptions. For this, we followed rats for six months post-injury, during which functional magnetic resonance imaging (fMRI) was conducted under light sedation, as well as diffusion tensor imaging (DTI) and positron emission tomography (PET). PET imaging with [18F]-FEPPA revealed neuroinflammation in the subacute stage in several ipsilateral thalamic nuclei, including the ventral posterior nucleus and lateral nucleus. In the fMRI analysis, we observed initial corticothalamic hypoconnectivity, which partially resolved by six months post-injury. DTI showed persistent increased mean, axial, and radial diffusivity in the ipsilateral thalamic nuclei from two months post-injury. Histological examination confirmed chronic thalamic neuroinflammation and neuronal loss eight months post-TBI. Correlation analyses showed that subacute thalamic neuroinflammation was associated with long-term structural and functional changes. These findings suggest that secondary thalamic inflammation contributes to enduring corticothalamic connectivity disruptions, which may underlie cognitive and sensorimotor deficits observed after TBI.