Potential influences of TBI on the course of PD. In the healthy brain the blood brain barrier (BBB) is intact, microglia are highly ramified and astrocytes are non-reactive and provide nourishment to neurons (a). In prodromal PD, degenerating neurons develop alpha synuclein pathology in the form of Lewy bodies and Lewy neurites, microglia become more amoeboid and phagocytic, BBB is compromised and peripheral immune cells infiltrate the brain where they become activated and take on a role similar to that of phagocytic resident microglia (b). After a TBI, BBB is temporarily permeabilized allowing infiltration of the peripheral immune cells, astrocytes become reactive and some neurons degenerate (c). In the clinical PD, the substantia nigra pars compacta is almost entirely devoid of dopaminergic neurons, and surviving neurons in nigra and other affected brain areas are burdened with alpha synuclein pathology while the areas vacated by dying neurons are filled with reactive astrocytes, microglia, and peripheral immune cells (d). Overlap in pathology induced by TBI and present in prodromal PD may allow for TBI to accelerate prodromal PD to clinical PD.