High erythropoietin levels are associated with low neurofilament light levels in simulated high altitude: a further hint for neuroprotection by erythropoietin.

Background: Erythropoietin (EPO) plays a crucial role in the early adaption to high altitude and is possibly involved in neuroprotection. Neurofilament light chain (NfL) is an established marker of neuroaxonal damage.

Objective: To investigate whether EPO dynamics in simulated high altitude are linked to neuroaxonal damage as measured by NfL.

Methods: Sixty-three healthy subjects were exposed to simulated altitude of 4,500 m for 12 h in a normobaric hypoxic chamber at the University of Innsbruck. Clinical data (heart rate, arterial oxygen saturation) were assessed before and 3 h after high altitude exposure; plasma samples were drawn before (measurement (M) 1) and after 12 h (M2). The levels of EPO and hypoxia-inducible factor (HIF)-1α were quantified using commercially available ELISA kits. NfL concentrations were measured using the Simoa SR-X Analyzer, and NfL Z scores calculated using age- and body mass index (BMI)-adjusted reference values.

Results: EPO significantly increased after 12 h (M2: 10.12 [7.86-14.06] mU/mL vs. M1: 4.17 [2.99-5.67] mU/mL,  < 0.001), while HIF-1α did not significantly change ( = 0.409). Subjects with high EPO levels at M2 showed significantly lower NfL concentrations (5.85 [4.15-6.85] pg/mL vs. 6.73 [4.70-8.64] pg/mL,  = 0.030) as well as lower NfL Z scores (0.64 [-0.88-1.17] vs. 0.95 [0.25-1.48],  = 0.040) than those with low EPO levels. The extent of heart rate increase showed a positive correlation with EPO levels at M2 (r = 0.322,  = 0.011).

Conclusion: Higher EPO concentrations were associated with lower NfL levels. This might further substantiate the hypothesis of a neuroprotective role of EPO.