Edwards Samantha, Corrigan Frances, Collins-Praino Lyndsey
Cognition, Ageing and Neurodegenerative Disease Laboratory, School of Biomedicine, The University of Adelaide, Adelaide, SA, 5005, Australia.
Head Injury Lab, School of Biomedicine, The University of Adelaide, Adelaide, SA, 5005, Australia.
Mol Neurobiol. 2025 Jun;62(6):7421-7444. doi: 10.1007/s12035-025-04706-x. Epub 2025 Feb 1.
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 α-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 α-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 α-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.
帕金森病（PD）的发展与创伤性脑损伤（TBI）病史有关，尽管其背后的驱动机制尚不清楚。值得注意的是，在PD和TBI的病理学之间已发现许多关键的相似之处；特别是，PD的特征是黑质（SN）中的多巴胺能神经元丧失，同时伴有多巴胺能信号传导的更广泛变化、蓝斑（LC）和去甲肾上腺素能系统的破坏，以及路易小体中聚集的α-突触核蛋白的积累，这种积累以一种刻板的模式在整个大脑中扩散。在损伤后急性期已观察到多巴胺能和去甲肾上腺素能系统的广泛破坏，包括SN和LC中神经元的进行性丧失，其中一些在TBI患者和临床前模型中也被长期观察到。此外，在整个大脑损伤后的急性期和慢性期都可见到α-突触核蛋白表达的变化，尽管对这些变化和病理扩散的详细表征有限。在这篇综述中，我们详细介绍了目前关于损伤后多巴胺能和去甲肾上腺素能破坏以及α-突触核蛋白病理学的文献，特别关注这些变化如何使个体易患长期病理和进行性神经退行性变，尤其是PD的发展。虽然越来越清楚TBI是PD发展的一个关键危险因素，但目前对TBI后神经退行性病理的理解，特别是损伤的慢性表现，仍存在重大差距。
