Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine, and PET, Copenhagen University Hospital Rigshospitalet, Glostrup, Denmark.
Department of Clinical Physiology, Nuclear Medicine, and PET, Copenhagen University Hospital Rigshospitalet , Copenhagen , Denmark.
J Appl Physiol (1985). 2018 Apr 1;124(4):1107-1116. doi: 10.1152/japplphysiol.00869.2017. Epub 2018 Jan 11.
Erythropoietin (EPO) is expressed in human brain tissue, but its exact role is unknown. EPO may improve the efficiency of oxidative metabolism and has neuroprotective properties against hypoxic injuries in animal models. We aimed to investigate the effect of recombinant human EPO (rHuEPO) administration on healthy cerebral metabolism in humans during normoxia and during metabolic stress by inhalation of 10% O hypoxic air. Twenty-four healthy men participated in a two-arm double-blind placebo-controlled trial. rHuEPO was administered as a low dose (5,000 IU) over 4 wk ( n = 12) or as a high dose (500 IU·kg body wt·day) for three consecutive days ( n = 12). Global cerebral blood flow (CBF) and metabolic rate of glucose (CMR) were measured with positron emission tomography. CBF, metabolic rate of oxygen ([Formula: see text]), and cerebral lactate concentration were measured by magnetic resonance imaging and spectroscopy. Low-dose treatment increased hemoglobin and was associated with a near-significant decrease in CBF during baseline normoxia. High-dose treatment caused no change in CBF. Neither treatment had an effect on normoxia CMR, [Formula: see text], or lactate concentration or an effect on the cerebral metabolic response to inhalation of hypoxic air. In conclusion, the study found no evidence for a direct effect of rHuEPO on cerebral metabolism. NEW & NOTEWORTHY We demonstrate with magnetic resonance imaging and positron emission tomography that administration of erythropoietin does not have a substantial direct effect on healthy human resting cerebral blood flow or effect on cerebral glucose and oxygen metabolism. Also, administration of erythropoietin did not have a direct effect on the metabolic response to acute hypoxic stress in healthy humans, and a suggested neuroprotective effect from erythropoietin is therefore likely not a direct effect of erythropoietin on cerebral metabolism.
促红细胞生成素 (EPO) 在人体脑组织中表达，但确切作用尚不清楚。EPO 可能提高氧化代谢效率，并具有动物模型中抗缺氧损伤的神经保护特性。我们旨在研究在常氧和吸入 10% O 低氧空气的代谢应激下，重组人促红细胞生成素 (rHuEPO) 给药对健康人脑代谢的影响。24 名健康男性参与了一项双臂、双盲、安慰剂对照试验。rHuEPO 以低剂量（5000IU）给药 4 周（n=12）或高剂量（500IU·kg 体重·天）连续 3 天给药（n=12）。使用正电子发射断层扫描测量全脑血流 (CBF) 和葡萄糖代谢率 (CMR)。通过磁共振成像和光谱测量 CBF、氧代谢率 ([Formula: see text]) 和脑乳酸浓度。低剂量治疗增加了血红蛋白，并与基线常氧时 CBF 接近显著降低相关。高剂量治疗对 CBF 没有影响。两种治疗均未影响常氧 CMR、[Formula: see text] 或乳酸浓度，也未影响吸入低氧空气时的脑代谢反应。总之，该研究未发现 rHuEPO 对脑代谢有直接影响的证据。新内容和值得注意的内容：我们通过磁共振成像和正电子发射断层扫描证明，促红细胞生成素的给药对健康人静息大脑血液流动没有实质性的直接影响，也不会影响大脑葡萄糖和氧气代谢。此外，促红细胞生成素的给药对健康人急性低氧应激的代谢反应没有直接影响，因此促红细胞生成素的神经保护作用可能不是促红细胞生成素对大脑代谢的直接作用。
