No evidence for direct effects of recombinant human erythropoietin on cerebral blood flow and metabolism in healthy humans

Abstract

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.

Higher physiological vulnerability to hypoxic exposure with advancing age in the human brain

“…Data reported in this study were obtained from healthy control subjects in multiple studies on the effect of inhalation of hypoxic air as follows: patients with obstructive sleep apnea (study A), 23 patients with migraine (study B), 24,25 healthy subjects treated with erythropoietin (study C), 17,26 freedivers (study D), 16 and a pilot study on healthy subjects (study E). By combining data from multiple studies, we obtained sufficient power of the statistics to examine the subtle effects from normal aging.…”

Age-related decline in cerebral oxygen consumption in multiple sclerosis

“…Haemoglobin was set to 9 mmol/l for all subjects, and arterial oxygen saturation was set to 98% for all subjects, since previous studies have shown that these do not differ significantly between MS and healthy controls. 32 We measured SvO 2 in the superior sagittal sinus using a susceptibility-based oximetry (SBO) MRI technique. 33 This technique utilises venous blood, which has a different magnetic susceptibility than brain tissue, and this difference is related to oxygen saturation.…”

Effects of Recombinant Human Erythropoietin on Inflammatory Factors in Rats with Traumatic Brain Injury

“…Recombinant human erythropoietin (rhEPO) is a drug commonly used for the treatment of renal insufficiencyinduced anemia in clinical practice. A pharmacological study proved that rhEPO can resist oxidation and apoptosis and promote nerve cell regeneration [6] . A recent study proved that rhEPO was able to protect brain tissues in TBI and had great potential in treating neurological diseases including stroke, cerebral hemorrhage and TBI [7] .…”