Plog Benjamin A, Dashnaw Matthew L, Hitomi Emi, Peng Weiguo, Liao Yonghong, Lou Nanhong, Deane Rashid, Nedergaard Maiken
Center for Translational Neuromedicine, Department of Neurosurgery and Department of Pathology, University of Rochester Medical Center, Rochester, New York 14642.
Center for Translational Neuromedicine, Department of Neurosurgery and.
J Neurosci. 2015 Jan 14;35(2):518-26. doi: 10.1523/JNEUROSCI.3742-14.2015.
The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity.
创伤性脑损伤（TBI）的非特异性和多变性表现促使人们积极寻找能够客观预测损伤严重程度的血液生物标志物。然而，目前尚不清楚创伤性脑组织释放的胞质蛋白是如何进入外周血的。在此，我们在小鼠TBI模型中表明，脑脊液通过最近发现的类淋巴途径流动，经颈淋巴管将生物标志物转运至血液。对类淋巴活动进行的临床相关操作，包括睡眠剥夺和脑池切开术，抑制或消除了TBI诱导的血清S100β、GFAP和神经元特异性烯醇化酶的升高。我们得出结论，常规的TBI患者管理可能会限制基于血液的生物标志物的临床应用，因为它们从脑到血的转运依赖于类淋巴活动。
