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bioRxiv · 10.1101/577130

Human recombinant erythropoietin improves motor function in rats with spinal cord compression myelopathy

Tanaka, T.·Murata, H.·Miyazaki, R.·Yoshizumi, T.·Sato, M.·Ohtake, M.·Tateishi, K.·Kim, P.·Yamamoto, T.
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Abstract

OBJECTIVEErythropoietin (EPO) is a clinically available hematopoietic cytokine. The aim of this study was to evaluate the effect of EPO on a rat model of cervical cord compression myelopathy and to explore the possibility of its use as a pharmacological treatment.\n\nMETHODSTo produce the chronic cervical cord compression model, thin polyurethane sheets were implanted under the C5-C6 laminae of rats and gradually expanded due to water absorption. In this model, motor functions significantly declined from 7 weeks after surgery. Based on the result, EPO administration was started 8 weeks after surgery. Motor function as seen with rotarod performance and grip strength was measured 16 weeks after surgery, and then motor neurons were stained with H-E and NeuN staining, and counted. Apoptotic cell death was assessed with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining. To assess transfer of EPO into spinal cord tissue, the EPO level in spinal cord tissue was measured with an enzyme-linked immunosorbent assay for each group after subcutaneous injection of EPO.\n\nRESULTSHigh-dose EPO (5000 IU/kg) administered from 8 weeks after surgery markedly restored and maintained motor function in the Compression groups (P < 0.01). EPO significantly prevented loss of motor neurons in the anterior horn (P < 0.05) and significantly decreased the number of TUNEL-positive apoptotic cells (P < 0.05). The EPO level in spinal cord tissue was significantly higher in the High-dose EPO group than other groups.\n\nCONCLUSIONSEPO improves motor function in rats with progressive chronic compression myelopathy. EPO protects anterior horn motor neurons and inhibits neuronal cell apoptosis in spinal cord compression. The neuroprotective effects can be produced through transfer of EPO into spinal cord tissue. These findings suggest that EPO has high potential as a treatment for developing compression myelopathy.

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Tanaka, T., Murata, H., Miyazaki, R., Yoshizumi, T., Sato, M., Ohtake, M., Tateishi, K., Kim, P., Yamamoto, T.. 2019-03-13. Human recombinant erythropoietin improves motor function in rats with spinal cord compression myelopathy. https://doi.org/10.1101/577130

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