Traumatic brain injury‐related inflammatory projection: beyond local inflammatory responses

Acute neuroinflammation induced by microglial activation is key for repair and recovery after traumatic brain injury (TBI) and could be necessary for the clearance of harmful substances, such as cell debris. However, recent clinical and preclinical data have shown that TBI causes chronic neuroinflammation, lasting many years in some cases, and leading to chronic neurodegeneration, dementia, and encephalopathy. To evaluate neuroinflammation in vivo, positron‐emission tomography has been used to target translocator protein, which is upregulated in activated glial cells. Such studies have suggested that remote neuroinflammation induced by regional microglia persists even after reduced inflammatory responses at the injury site. Furthermore, unregulated inflammatory responses are associated with neurodegeneration. Therefore, elucidation of the role of neuroinflammation in TBI pathology is essential for developing new therapeutic targets for TBI. Treatment of associated progressive disorders requires a deeper understanding of how inflammatory responses to injury are triggered, sustained, and resolved and how they impact neuronal function. In this review, we provide a general overview of the dynamics of immune responses to TBI, from acute to chronic neuroinflammation. We discuss the clinical significance of remote ongoing neuroinflammation, termed “brain injury‐related inflammatory projection”. We also highlight positron‐emission tomography imaging as a promising approach needing further development to facilitate an understanding of post‐TBI inflammatory and neurodegenerative processes and to monitor the clinical effects of corresponding new therapeutic strategies.