Fig. 2

Neuroinflammatory process after the occurrence of TBI and its long-term consequences. After TBI occurs, it can lead to a range of primary (e.g., damage to blood vessels and cell membranes) or secondary (e.g., ion imbalance, calcium overload, and mitochondrial dysfunction) injuries. These injuries together lead to mitochondrial stress cytotoxicity and secondary damage to the vascular system. Subsequently, astrocytes and microglia are activated, and immune cells in the blood vessels are recruited. Microglia can differentiate into M1 and M2 phenotypes, which can produce pro-inflammatory or anti-inflammatory cytokines in response to cytokines such as interferon-γ (IFN-γ), interleukin-4 (IL-4) and IL-13. Microglia itself also divide and play a role in phagocytosis. These neuroinflammatory mechanisms can promote the formation of new synapses, which is conducive to the self-repair of the nervous system. Long-term chronic inflammation can also lead to neurodegeneration, resulting in a series of irreversible pathological changes (such as Tau protein hyperphosphorylation, Aβ plaque formation, TDP-43 and α -synuclein deposition, etc.). Over the years, neurodegeneration can eventually lead to dementia. Solid black and red arrows indicate associations of pathological mechanisms or clinical manifestations, dashed black arrows indicate relationships among subtypes, and dashed red arrows indicate possible aetiology of CTE. TBI traumatic brain injury, CNS central nervous system, Aβ amyloid-β, TDP-43 trans-reaction DNA-binding protein 43 kD