Inflammatory projections after focal brain injury trigger neuronal network disruption: An 18F-DPA714 PET study in mice

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.
Graphical abstract TSPO-PET detects two types of distinct inflammation occur after focal cortical injury: 1) cortical lesions respecting stable lesion boundaries, complete scars and rapid neuronal loss of injured tracts, and 2) thalamic lesions exhibiting delayed inflammatory response and long-term neuronal degeneration of uninjured tractsUnlabelled Image
Highlights • TSPO-PET tomography enables the assessment of longitudinal neuronal inflammation • Inflammatory responses at the cortical injury site diminish after about 1 week • The ipsilateral thalamus exhibits remote neuroinflammation for up to 14 weeks • Microglial activation is associated with remote chronic degeneration • Inflammation expands to remote sites via damaged cortico-thalamic projections