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  4. Spinal Stroke: Outcome Attenuation by Erythropoietin and Carbamylated Erythropoietin and Its Prediction by Sphingosine-1-Phosphate Serum Levels in Mice

Spinal Stroke: Outcome Attenuation by Erythropoietin and Carbamylated Erythropoietin and Its Prediction by Sphingosine-1-Phosphate Serum Levels in Mice

Int. J. Mol. Sci., 2022 · DOI: 10.3390/ijms23179558 · Published: August 23, 2022

Spinal Cord InjuryPharmacologyGenetics

Simple Explanation

This study investigates whether erythropoietin (EPO) or carbamylated EPO (cEPO) can reduce neuronal damage caused by spinal ischemia-reperfusion sequence (IRS) in mice by modulating the unfolded protein response (UPR). The study also examines if serum levels of sphingosine-1-phosphate (S1P) correlate with neurological function after spinal cord injury (SCI). Spinal strokes can lead to severe spinal cord injury, and while various strategies have been tested, no generally accepted regimen exists to protect the spinal cord during aortic procedures.

Study Duration
Not specified
Participants
12-month-old male C57BL/6 mice
Evidence Level
Not specified

Key Findings

  • 1
    Treatment with rhEPO and cEPO-Fc significantly improves the neurological outcome of mice after spinal cord ischemia.
  • 2
    Significantly more intact neurons were found in both EPO treatment groups after 96 hours compared to the control group.
  • 3
    Animals with better locomotory behavior had significantly higher serum levels of S1P.

Research Summary

This study investigates the effects of recombinant human erythropoietin (rhEPO) and carbamylated EPO (cEPO-Fc) on mice after spinal cord ischemia (SCI) and the prognostic value of sphingosin-1-phosphate (S1P). The data indicate that rhEPO and cEPO-Fc have protective effects on the clinical outcome and neuronal tissue of mice after SCI and that the ER is involved in the molecular mechanisms. Moreover, serum S1P may predict the severity of impairment after SCI.

Practical Implications

Therapeutic Potential of EPO

Erythropoietin and its carbamylated derivatives may attenuate damage after spinal cord ischemia, suggesting a therapeutic avenue.

Prognostic Marker

Early high S1P serum levels after SCI correlate with good neurological outcomes, suggesting S1P might be useful as a prognostic marker after SCI.

Further Research

Further investigation in patients might also identify individuals that benefit from the activation of S1PR1 by FTY-720 early after ischemic damage.

Study Limitations

  • 1
    The underlying pathway by which rhEPO and cEPO-Fc protect against SCI remains unclear.
  • 2
    The exact processes that are involved in mediating the beneficial effects of rhEPO and cEPO-Fc remain to be fully elucidated.
  • 3
    Further studies in animal models and especially in humans must follow to further investigate the potential of S1P as a biomarker.

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