Huang Suna, Li Su, Feng Hua, Chen Yujie
Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing, China.
State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing, China.
Front Neurosci. 2021 Mar 16;15:587197. doi: 10.3389/fnins.2021.587197. eCollection 2021.
Traumatic brain injury (TBI) is one of the most harmful forms of acute brain injury and predicted to be one of the three major neurological diseases that cause neurological disabilities by 2030. A series of secondary injury cascades often cause cognitive dysfunction of TBI patients leading to poor prognosis. However, there are still no effective intervention measures, which drive us to explore new therapeutic targets. In this process, the most part of mild traumatic brain injury (mTBI) is ignored because its initial symptoms seemed not serious. Unfortunately, the ignored mTBI accounts for 80% of the total TBI, and a large part of the patients have long-term cognitive dysfunction. Iron deposition has been observed in mTBI patients and accompanies the whole pathological process. Iron accumulation may affect long-term cognitive dysfunction from three pathways: local injury, iron deposition induces tau phosphorylation, the formation of neurofibrillary tangles; neural cells death; and neural network damage, iron deposition leads to axonal injury by utilizing the iron sensibility of oligodendrocytes. Thus, iron overload and metabolism dysfunction was thought to play a pivotal role in mTBI pathophysiology. Cerebrospinal fluid-contacting neurons (CSF-cNs) located in the ependyma have bidirectional communication function between cerebral-spinal fluid and brain parenchyma, and may participate in the pathway of iron-induced cognitive dysfunction through projected nerve fibers and transmitted factor, such as 5-hydroxytryptamine, etc. The present review provides an overview of the metabolism and function of iron in mTBI, and to seek a potential new treatment target for mTBI with a novel perspective through combined iron and CSF-cNs.
创伤性脑损伤（TBI）是急性脑损伤中危害最大的形式之一，预计到2030年将成为导致神经功能障碍的三大主要神经疾病之一。一系列继发性损伤级联反应常导致TBI患者出现认知功能障碍，预后不良。然而，目前仍没有有效的干预措施，这促使我们探索新的治疗靶点。在此过程中，轻度创伤性脑损伤（mTBI）的大部分情况被忽视，因为其初始症状似乎不严重。不幸的是，被忽视的mTBI占TBI总数的80%，且很大一部分患者存在长期认知功能障碍。在mTBI患者中已观察到铁沉积，且其伴随整个病理过程。铁蓄积可能从三个途径影响长期认知功能障碍：局部损伤，铁沉积诱导tau蛋白磷酸化，形成神经原纤维缠结；神经细胞死亡；以及神经网络损伤，铁沉积通过利用少突胶质细胞的铁敏感性导致轴突损伤。因此，铁过载和代谢功能障碍被认为在mTBI病理生理过程中起关键作用。位于室管膜的脑脊液接触神经元（CSF-cNs）在脑脊液与脑实质之间具有双向通讯功能，可能通过投射神经纤维和传递因子（如5-羟色胺等）参与铁诱导的认知功能障碍途径。本综述概述了mTBI中铁的代谢和功能，并通过结合铁和CSF-cNs从新的角度寻找mTBI潜在的新治疗靶点。
