University of Windsor, Faculty of Human Kinetics, Department of Kinesiology, Windsor, ON, Canada.
University of British Columbia, Kelowna, Centre for Heart Lung and Vascular Health, Vancouver, BC, Canada.
J Appl Physiol (1985). 2021 Mar 1;130(3):792-800. doi: 10.1152/japplphysiol.00645.2020. Epub 2021 Jan 14.
With growing use for hyperthermia as a cardiovascular therapeutic, there is surprisingly little information regarding the acute effects it may have on the integrity of the neurovascular unit (NVU). Indeed, relying on animal data would suggest hyperthermia comparable to levels attained in thermal therapy will disrupt the blood-brain barrier (BBB) and damage the cerebral parenchymal cells. We sought to address the hypothesis that controlled passive hyperthermia is not sufficient to damage the NVU in healthy humans. Young men ( = 11) underwent acute passive heating until +2°C or absolute esophageal temperature of 39.5°C. The presence of BBB opening was determined by trans-cerebral exchange kinetics (radial-arterial and jugular venous cannulation) of S100B. Neuronal parenchymal damage was determined by the trans-cerebral exchange of tau protein, neuron-specific enolase (NSE), and neurofilament-light protein (NF-L). Cerebral blood flow to calculate exchange kinetics was measured by duplex ultrasound of the right internal carotid and left vertebral artery. Passive heating was performed via a warm-water perfused suit. In hyperthermia, there was no increase in the cerebral exchange of S100B ( = 0.327), tau protein ( = 0.626), NF-L ( = 0.447), or NSE ( = 0.908) suggesting the +2°C core temperature is not sufficient to acutely stress the NVU in healthy men. However, there was a significant condition effect ( = 0.028) of NSE, corresponding to a significant increase in arterial ( = 0.023) but not venous ( = 0.173) concentrations in hyperthermia, potentially indicating extra-cerebral release of NSE. Collectively, results from the present study support the notion that in young men there is little concern for NVU damage with acute hyperthermia of +2 °C. The acute effects of passive whole-body hyperthermia on the integrity of the neurovascular unit (NVU) in humans have remained unclear. We demonstrate that passive heating for ∼1 h until an increase of +2°C esophageal temperature in healthy men does not increase the cerebral release of neuronal parenchymal stress biomarkers, suggesting the NVU integrity is maintained. This preliminary study indicates passive heating is safe for the brain, at least in young healthy men.
随着高热作为心血管治疗的应用越来越广泛，令人惊讶的是，关于它可能对神经血管单元 (NVU) 完整性的急性影响的信息却很少。事实上，仅依靠动物数据表明，与热疗中达到的水平相当的热疗会破坏血脑屏障 (BBB) 并损害脑实质细胞。我们试图验证这样一个假设，即控制的被动升温不足以在健康人体中损害 NVU。11 名年轻男性接受急性被动加热，直到体温升高 2°C 或食管温度达到 39.5°C。BBB 开放的存在通过 S100B 的跨脑交换动力学（桡动脉和颈内静脉插管）来确定。神经元实质损伤通过 tau 蛋白、神经元特异性烯醇化酶 (NSE) 和神经丝轻蛋白 (NF-L) 的跨脑交换来确定。为了计算交换动力学，通过右侧颈内动脉和左侧椎动脉的双功超声测量脑血流。通过温水灌注服进行被动加热。在发热时，S100B（= 0.327）、tau 蛋白（= 0.626）、NF-L（= 0.447）和 NSE（= 0.908）的脑交换均未增加，表明核心体温升高 2°C 不足以急性应激健康男性的 NVU。然而，NSE 存在显著的条件效应（= 0.028），对应于发热时动脉（= 0.023）但不是静脉（= 0.173）浓度的显著增加，这可能表明 NSE 的脑外释放。总的来说，本研究的结果支持这样一种观点，即在年轻男性中，急性体温升高 2°C 时，NVU 损伤的可能性很小。被动全身热疗对人类神经血管单元 (NVU) 完整性的急性影响仍不清楚。我们证明，在健康男性中，被动加热约 1 小时，直到食管温度升高 2°C，不会增加脑实质应激生物标志物的释放，这表明 NVU 完整性得到维持。这项初步研究表明，被动加热对大脑是安全的，至少在年轻健康男性中是如此。
