Abstract
Due to the heterogeneous pathology of traumatic brain injury (TBI), the exact mechanism of how initial brain damage leads to chronic inflammation and its effects on the whole brain remain unclear. Here, we report on long-term neuroinflammation, remote from the initial injury site, even after subsiding of the original inflammatory response, in a focal TBI mouse model. The use of translocator protein-positron emission tomography in conjunction with specialised magnetic resonance imaging modalities enabled us to visualize “previously undetected areas” of spreading inflammation after focal cortical injury. These clinically available modalities further revealed the pathophysiology of thalamic neuronal degeneration occurring as resident microglia sense damage to corticothalamic neuronal tracts and become activated. The resulting microglial activation plays a major role in prolonged inflammatory processes, which are deleterious to the thalamic network. In light of the association of this mechanism with neuronal tracts, we propose it can be termed “brain injury related inflammatory projection”. Our findings on multiple spatial and temporal scales provide insight into the chronic inflammation present in neurodegenerative diseases after TBI.
Highlights
Traumatic brain injury (TBI) is an increasingly prominent public health and societal issue worldwide (Majdan et al, 2016)
Some experimental and clinical evidence suggests that traumatic brain injury (TBI) can initiate chronic biochemical processes that lead to prolonged neuroinflammation or microglial activation, contributing to chronic neuropathy (Johnson et al, 2013; Loane et al, 2014)
We found that translocator protein (TSPO) mainly co-localised with amoeboid CD11bpositive microglia/macrophages and weakly with GFAP-positive astrocytes (Fig. 2A and Supplemental Fig. 3)
Summary
Traumatic brain injury (TBI) is an increasingly prominent public health and societal issue worldwide (Majdan et al, 2016). It is associated with increased mobility, mortality (Brooks et al, 2013), and decreased life expectancy (Brooks et al, 2015). Previous history of acute mild TBI is the strongest risk factor for neurodegenerative conditions among contact sport athletes and war veterans (Nordström et al, 2014; Vincent et al, 2014) and is a suspected factor in various chronic neurodegenerative conditions, including traumatic encephalopathy, Alzheimer's, and Parkinson's disease (Chauhan, 2014). Traditional histological and immunohistochemical approaches have identified limited aspects of acute and chronic inflammation in the brain post-TBI (Johnson et al, 2013). Due to TBI variability and/or patient heterogeneity, the exact mechanism underlying brain damagerelated chronic inflammation and its effects on neurodegeneration
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
