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


Autoři: Takahiro Tanaka aff001;  Hidetoshi Murata aff001;  Ryohei Miyazaki aff001;  Tetsuya Yoshizumi aff001;  Mitsuru Sato aff001;  Makoto Ohtake aff001;  Kensuke Tateishi aff001;  Phyo Kim aff002;  Tetsuya Yamamoto aff001
Působiště autorů: Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan aff001;  Department of Neurosurgery, Dokkyo Medical University, Tochigi, Japan aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0214351

Souhrn

Objective

Erythropoietin (EPO) is a clinically available hematopoietic cytokine. EPO has shown beneficial effects in the context of spinal cord injury and other neurological conditions. The aim of this study was to evaluate the effect of EPO on a rat model of spinal cord compression-induced cervical myelopathy and to explore the possibility of its use as a pharmacological treatment.

Methods

To develop the compression-induced cervical myelopathy model, an expandable polymer was implanted under the C5-C6 laminae of rats. EPO administration was started 8 weeks after implantation of a polymer. Motor function of rotarod performance and grip strength was measured after surgery, and motor neurons were evaluated with H-E, NeuN and choline acetyltransferase staining. Apoptotic cell death was assessed with TUNEL and Caspase-3 staining. The 5HT, GAP-43 and synaptophysin were evaluated to investigate the protection and plasticity of axons. Amyloid beta precursor protein (APP) was assessed to evaluate axonal injury.

To assess transfer of EPO into spinal cord tissue, the EPO levels in spinal cord tissue were measured with an ELISA for each group after subcutaneous injection of EPO.

Results

High-dose EPO maintained motor function in the compression groups. EPO significantly prevented the loss of motor neurons and significantly decreased neuronal apoptotic cells. Expression of 5HT and synaptophysin was significantly preserved in the EPO group. APP expression was partly reduced in the EPO group. The EPO levels in spinal cord tissue were significantly higher in the high-dose EPO group than other groups.

Conclusion

EPO improved motor function in rats with compression-induced cervical myelopathy. EPO suppressed neuronal cell apoptosis, protected motor neurons, and induced axonal protection and plasticity. The neuroprotective effects were produced following transfer of EPO into the spinal cord tissue. These findings suggest that EPO has high potential as a treatment for degenerative cervical myelopathy.

Klíčová slova:

Apoptosis – Axons – Cell staining – Central nervous system – Motor neurons – Surgical and invasive medical procedures – Anterior horn cells


Zdroje

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