爆炸冲击波性脑损伤的发生机制和生物标志物研究进展

Research progress on the pathogenesis and biomarkers of blast-induced traumatic brain injury

爆炸冲击波性脑损伤(blast-induced traumatic brain injury,bTBI)是由爆炸时的冲击波对颅脑造成的损伤效应,伤者可表现出不同程度的躯体和行为障碍以及远期认知功能损害,是战时最常见的脑损伤类型。bTBI的发生机制复杂且尚未完全阐明。爆炸产生的冲击波作用于头部表面并在颅内传播,造成颅脑弥漫性损伤,从病理学层面可将bTBI分为原发性损伤和继发性损伤。冲击波的机械致伤效应会造成脑内结构的原发性受损,通常不可逆,只能采取有效的预防措施减少伤害。原发性损伤可引发一系列复杂的继发性级联反应,包括突触功能障碍、兴奋性毒性损伤、血脑屏障破坏、脑膜淋巴系统功能障碍、神经炎症、线粒体功能障碍、氧化应激反应、tau蛋白过度磷酸化和淀粉样蛋白-β病理改变等,可持续至伤后数天甚至慢性阶段,为临床治疗提供了干预的时间窗。轻度bTBI临床表现异质性高,影像学表现常呈阴性,早期诊断困难。但近年来bTBI的血液生物标志物取得长足进展,包括泛素C末端水解酶L1、神经元特异性烯醇化酶、神经丝蛋白轻链、磷酸化tau蛋白、髓鞘碱性蛋白、胶质纤维酸性蛋白、S100钙结合蛋白B和其他新兴生物标志物等,有望成为影像学阴性的bTBI的早期诊断和预后判断的潜在生物标志物。综上,本文重点综述了近年来关于bTBI的发生机制和生物标志物研究的前沿进展,并展望了未来的研究方向,以期为探索bTBI的发生机制、早期诊断策略和干预靶点提供新思路。

Blast-induced traumatic brain injury(bTBI)is defined as the damaging effect of the shock wave on the brain,which may cause behavioral impairment,physical symptoms and long-term cognitive impairment.Statistically,bTBI is the most common type of traumatic brain injury in combatants,but the mechanism has not been fully elucidated so far because of the high complexity of bTBI.When the shock wave produced during explosions acts on the surface of the skull and propagates within the head,it can lead to a diffuse damage to the brain.In terms of pathological mechanism,bTBI includes two aspects:primary injury and secondary injury.The mechanical injury effect of the shock wave generated by explosions can cause the primary injury of craniocerebral structures,which is usually irreversible and can be only prevented with effective measures.And the secondary injuries will be triggered by the primary injury after bTBI,which involve a series of complex cascades including synaptic dysfunction,excitotoxic injury,blood-brain barrier disruption,meningeal lymphatic system dysfunction,neuroinflammation,mitochondrial dysfunction,oxidative stress,tau protein hyperphosphorylation and amyloid-βpathological changes.And it can last for some time or even extend into the chronic stage after injury,providing a critical window for intervention.It is difficult to diagnose mild bTBI due to the high heterogeneity of clinical symptoms and the positive imaging manifestations.However,great progresses have been made in the research of blood biomarkers of bTBI in recent years,such as ubiquitin carboxyl-terminal hydrolase L1,neuron-specific enolase,neurofilament protein-light,hyperphosphorylated tau protein,myelin basic protein,glial fibrillary acidic protein,S100 calcium-binding protein B and other novel biomarkers.All of the above-mentioned biomarkers are expected to be effective means of early diagnosis and prognosis judgment of imagingnegative bTBI.In conclusion,this review focuses on the frontier progress of the pathogenesis and biomarkers of bTBI,and looks forward to future research directions in order to provide more new ideas for exploring the pathogenesis,early diagnosis strategies as well as intervention targets of bTBI.