Lozano Diego, Gonzales-Portillo Gabriel S, Acosta Sandra, de la Pena Ike, Tajiri Naoki, Kaneko Yuji, Borlongan Cesar V
Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
Neuropsychiatr Dis Treat. 2015 Jan 8;11:97-106. doi: 10.2147/NDT.S65815. eCollection 2015.
Traumatic brain injury (TBI) is a serious public health problem accounting for 1.4 million emergency room visits by US citizens each year. Although TBI has been traditionally considered an acute injury, chronic symptoms reminiscent of neurodegenerative disorders have now been recognized. These progressive neurodegenerative-like symptoms manifest as impaired motor and cognitive skills, as well as stress, anxiety, and mood affective behavioral alterations. TBI, characterized by external bumps or blows to the head exceeding the brain's protective capacity, causes physical damage to the central nervous system with accompanying neurological dysfunctions. The primary impact results in direct neural cell loss predominantly exhibiting necrotic death, which is then followed by a wave of secondary injury cascades including excitotoxicity, oxidative stress, mitochondrial dysfunction, blood-brain barrier disruption, and inflammation. All these processes exacerbate the damage, worsen the clinical outcomes, and persist as an evolving pathological hallmark of what we now describe as chronic TBI. Neuroinflammation in the acute stage of TBI mobilizes immune cells, astrocytes, cytokines, and chemokines toward the site of injury to mount an antiinflammatory response against brain damage; however, in the chronic stage, excess activation of these inflammatory elements contributes to an "inflamed" brain microenvironment that principally contributes to secondary cell death in TBI. Modulating these inflammatory cells by changing their phenotype from proinflammatory to antiinflammatory would likely promote therapeutic effects on TBI. Because neuroinflammation occurs at acute and chronic stages after the primary insult in TBI, a treatment targeting neuroinflammation may have a wider therapeutic window for TBI. To this end, a better understanding of TBI etiology and clinical manifestations, especially the pathological presentation of chronic TBI with neuroinflammation as a major component, will advance our knowledge on inflammation-based disease mechanisms and treatments.
创伤性脑损伤（TBI）是一个严重的公共卫生问题，每年有140万美国公民因之前往急诊室就诊。尽管TBI传统上被认为是一种急性损伤，但现在人们已经认识到它会出现类似于神经退行性疾病的慢性症状。这些渐进性的神经退行性样症状表现为运动和认知技能受损，以及压力、焦虑和情绪情感行为改变。TBI的特征是头部受到的外部撞击或打击超过了大脑的保护能力，导致中枢神经系统受到物理损伤并伴有神经功能障碍。主要影响导致直接神经细胞损失，主要表现为坏死性死亡，随后是一系列继发性损伤级联反应，包括兴奋性毒性、氧化应激、线粒体功能障碍、血脑屏障破坏和炎症。所有这些过程都会加剧损伤，恶化临床结果，并持续作为我们现在所描述的慢性TBI不断演变的病理特征。TBI急性期的神经炎症会促使免疫细胞、星形胶质细胞、细胞因子和趋化因子向损伤部位聚集，以对脑损伤发起抗炎反应；然而，在慢性期，这些炎症成分的过度激活会导致大脑微环境“发炎”，这主要导致TBI中的继发性细胞死亡。通过将这些炎症细胞的表型从促炎转变为抗炎来调节它们，可能会促进对TBI的治疗效果。由于神经炎症发生在TBI原发性损伤后的急性和慢性阶段，针对神经炎症的治疗可能对TBI有更广泛的治疗窗口。为此，更好地了解TBI的病因和临床表现，特别是以神经炎症为主要成分的慢性TBI的病理表现，将推进我们对基于炎症的疾病机制和治疗的认识。
