The synapse in traumatic brain injury.
The synapse in traumatic brain injury.
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DOI：
10.1093/brain/awaa321
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发表时间：
2021-02-12
期刊：
影响因子：
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通讯作者：
Grant SGN
中科院分区：
文献类型：
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作者：
Jamjoom AAB;Rhodes J;Andrews PJD;Grant SGN
创伤性脑损伤是死亡和残疾的主要原因，也是晚年痴呆的危险因素。Jamjoom等人综述了突触在TBI病理生理学中的作用，重点关注继发性损伤过程的汇合，包括轴突损伤、兴奋性毒性、炎症和氧化应激。创伤性脑损伤（TBI）是全球死亡和残疾的主要原因，也是晚年痴呆的危险因素。对TBI的病理生理学的研究集中在损伤对神经元的影响上。然而，最近的进展表明，TBI通过直接的机械损伤和随后的继发性损伤过程的组合对突触结构和功能产生重大影响，导致突触丧失。在这篇综述中，我们强调了突触在TBI病理生理学中的作用，重点是多个继发性损伤过程的汇合，包括兴奋性毒性，炎症和氧化应激。初级损伤在这些次级过程中触发了一系列事件，我们讨论了在突触处发生的复杂相互作用。我们还研究了突触如何受到创伤性轴突损伤的影响，以及它在TBI后tau蛋白扩散中可能发挥的作用。我们认为星形胶质细胞通过介导突触丢失和恢复起着至关重要的作用。最后，我们强调了该领域的最新进展，包括突触分子成像，流体生物标志物和治疗。特别是，我们讨论了我们对突触多样性的理解的进展，并建议突触映射的新技术可能被证明是有用的，在识别突触是脆弱的或耐TBI。
Traumatic brain injury is a leading cause of death and disability and is a risk factor for dementia later in life. Jamjoom et al. review the role of the synapse in TBI pathophysiology with a focus on the confluence of secondary injury processes including axonal injury, excitotoxicity, inflammation and oxidative stress. Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and is a risk factor for dementia later in life. Research into the pathophysiology of TBI has focused on the impact of injury on the neuron. However, recent advances have shown that TBI has a major impact on synapse structure and function through a combination of the immediate mechanical insult and the ensuing secondary injury processes, leading to synapse loss. In this review, we highlight the role of the synapse in TBI pathophysiology with a focus on the confluence of multiple secondary injury processes including excitotoxicity, inflammation and oxidative stress. The primary insult triggers a cascade of events in each of these secondary processes and we discuss the complex interplay that occurs at the synapse. We also examine how the synapse is impacted by traumatic axonal injury and the role it may play in the spread of tau after TBI. We propose that astrocytes play a crucial role by mediating both synapse loss and recovery. Finally, we highlight recent developments in the field including synapse molecular imaging, fluid biomarkers and therapeutics. In particular, we discuss advances in our understanding of synapse diversity and suggest that the new technology of synaptome mapping may prove useful in identifying synapses that are vulnerable or resistant to TBI.