Lasting Impact: Exploring the Brain Mechanisms that Link Traumatic Brain Injury to Parkinson's Disease

Development of Parkinson's Disease (PD) is linked with a history of traumatic brain injury (TBI), although the mechanisms driving this remain unclear. Of note, many key parallels have been identified between the pathologies of PD and TBI; in particular, PD is characterised by loss of dopaminergic neurons from the substantia nigra (SN), accompanied by broader changes to dopaminergic signalling, disruption of the Locus Coeruleus (LC) and noradrenergic system, and accumulation of aggregated alpha-synuclein in Lewy Bodies, which spreads in a stereotypical pattern throughout the brain. Widespread disruptions to the dopaminergic and noradrenergic systems, including progressive neuronal loss from the SN and LC, have been observed acutely following injury, some of which have also been identified chronically in TBI patients and preclinical models. Furthermore, changes to alpha-synuclein expression are also seen both acutely and chronically following injury throughout the brain, although detailed characterisation of these changes and spread of pathology is limited. In this review, we detail the current literature regarding dopaminergic and noradrenergic disruption and alpha-synuclein pathology following injury, with particular focus on how these changes may predispose individuals to prolonged pathology and progressive neurodegeneration, particularly the development of PD. While it is increasingly clear that TBI is a key risk factor for the development of PD, significant gaps remain in current understanding of neurodegenerative pathology following TBI, particularly chronic manifestations of injury.