Neuroprotective properties of erythropoietin (Epo) and its receptor (EpoR) in open spinal dysraphism (OSD): an investigation of EpoR expression in a rat OSD model, along with in vitro studies on the neuroprotective effects of Epo on rat spinal cord-derived neural progenitor cells.

PURPOSE: Research into treatment options that complement surgery for open spinal dysraphism (OSD) is necessary to further improve outcomes following prenatal or postnatal surgery. We investigated erythropoietin (Epo) and its receptor (EpoR) as a potential neuroprotective agent and target in OSD.

METHODS

Epo- and EpoR-expression was examined on mRNA and immunohistochemical level in neuroplacodes obtained from a rat retinoic acid-induced OSD model at E16, E18, E22. Neural progenitor cells (NPCs) derived from spinal cords of adult Long Evans rats were exposed to varying concentrations of human artificial amniotic fluid (aAF). Cytotoxicity assays were conducted to assess the impact of aAF exposure, with and without Epo. The influence of Epo on NPC's cellular marker expression was analyzed using qRT-PCR.

RESULTS

EpoR mRNA expression was elevated significantly on E18 and E22 in OSD- compared to control tissue. EpoR immunoreactivity exhibited consistent expression in ventral and dorsal horns, central canal, and ganglia. It co-stained with Hif-2α, β-III-tubulin, NeuN, and Musashi1. Exposure of NPCs to aAF reduced proliferation and increased death rates dose-dependently. Adding Epo significantly counteracted antiproliferative and cytotoxic aAF effects on NPCs, resulting in similar or lower death rates than those observed in untreated controls. Exposure of NPCs to aAF reduced their expression of neuronal markers. Adding Epo restored their differentiation capacities.

CONCLUSION

Induction of EpoR in neuroplacodes, its co-staining with neuronal and NPC markers, and the neuroprotective effects of Epo on aAF-treated NPCs in vitro establish Epo as a promising candidate for neuroprotective therapies that can supplement surgical measures for OSD.