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Research ArticleSpine
Open Access

Erythropoietin Promotes Functional Recovery and Enhances Nerve Regeneration after Peripheral Nerve Injury in Rats

Z.-S. Yin, H. Zhang and W. Gao
American Journal of Neuroradiology March 2010, 31 (3) 509-515; DOI: https://doi.org/10.3174/ajnr.A1820
Z.-S. Yin
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H. Zhang
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W. Gao
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    Fig 1.

    Photograph shows tubulation with a 7-mm-long interstump gap. The proximal and distal nerve stumps were joined to a 10-mm-long silicone rubber tube, leaving a 7-mm interstump gap. The ruler is graduated in millimeters.

  • Fig 2.
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    Fig 2.

    Comparison of the mean functional recovery of each group after sciatic nerve transection and repair. Functional analysis of neural regeneration was assessed at 4 and 8 weeks after surgery by using walking-track analysis. Measurements made from walking-track prints were then submitted to an SFI. Data are the mean ± SEM. The asterisk indicates P < .05 compared with the NGF group significance.

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    Fig 3.

    Effect of EPO administration on MNCV. At weeks 4 and 8 after surgery, MNCV was significantly lower in the NGF group than in the EPO group. There are statistically significant differences in MNCV between the 2 groups. Data are mean ± SEM. The asterisk indicates P < .05 compared with the NGF group.

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    Fig 4.

    The arrows demonstrate the thickness of scar tissue of nerve fiber bundles 8 weeks after surgery. A, A rat treated with NGF shows a very thick band of scar tissue surrounding fiber bundles. B, A rat treated with EPO shows very thin bands of scar tissue surrounding fiber bundles (hematoxylin-eosin stain, original magnification ×100).

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    Fig 5.

    Representative photomicrographs of regenerated sciatic nerve cross-sections. The modified Bielschowsky silver stain was used to visualize myelinated axons. A and B, Regeneration of myelinated axons at 4 weeks. C and D, Regeneration at 8 weeks. A−D, These photomicrographs demonstrated significantly better regeneration in the EPO group (B and D) compared with the NGF group (A and C). E, Quantitation of myelinated axon counts in regenerated sciatic nerve cross-sections is shown. There are statistically significant differences in myelinated axon counts between the 2 groups at 4 and 8 weeks after surgery. Data are the mean ± SEM. The asterisk indicates P < .05 compared with the NGF group significance (uranyl acetate-lead stain, original magnification ×400).

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    Fig 6.

    A and B, Representative ultrastructural imaging of cross-sections of nerve originally located 10-mm distal to the silicone rubber tube in the NGF and EPO groups respectively at week 8 after surgery. A, The NGF group shows lower myelin thickness and axonal diameter and fewer myelinated fibers. B, The EPO group shows higher myelin thickness and axonal diameter and more myelinated fibers. C and D, There are statistically significant differences in myelin thickness (C) and axonal diameter (D) between the 2 groups at 8 weeks after surgery. Data are the mean ± SEM. The asterisk indicates P < .05 compared with the NGF group significance.

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    Fig 7.

    Representative photomicrographs of immunohistochemical staining of PGP 9.5 in regenerated sciatic nerve cross-sections. Axons and the periphery of the axons show strong immunoreactivity. A and B, Expression of PGP 9.5 in immunopositive nerve fibers at 4 weeks. C and D, Expression of PGP 9.5 at week 8. A−F, Quantitative analysis by using MOD and IOD reveals that nerves treated with EPO (B and D) have significantly higher MOD (E) and IOD (F) compared with those in the NGF group (A and C), and there are statistically significant differences between the 2 groups at the 2 time points. Data are the mean ± SEM. The asterisk indicates P < .05. Double asterisks indicate P < .01 compared with the NGF group significance.

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    Table 1:

    Results of functional and electrophysiologic evaluation (mean ± SEM)

    4 Weeks8 Weeks
    SFIa
        NGF−79.98 ± 4.58−64.65 ± 4.11
        EPO−78.85 ± 3.87, P > .05−60.26 ± 2.91, P < .05
    MNCV (m/s)b
        NGF9.20 ± 1.0716.37 ± 3.40
        EPO10.60 ± 1.36, P < .0520.56 ± 4.18, P < .05
    • a The SFI studies at 8 weeks postsurgery demonstrated better improvement in nerve function in rats that received EPO.

    • b Rats treated with EPO showed better results than those of the NGF group at the 2 time points.

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    Table 2:

    Results of histomorphometry and electron microscopy and immunohistochemistry (mean ± SEM)

    4 Weeks8 Weeks
    Myelin thickness (μm)a
        NGF0.43 ± 0.09
        EPO0.57 ± 0.08, P < .05
    Axon diameter (μm)a
        NGF1.73 ± 0.51
        EPO2.39 ± 0.32, P < .05
    Myelinated axon counts (at original magnification ×400)b
        NGF17.56 ± 4.1949.30 ± 9.56
        EPO22.90 ± 5.24, P < .0558.00 ± 7.73, P < .05
    MOD (at original magnification ×400)b
        NGF0.2173 ± 0.02570.3089 ± 0.0343
        EPO0.2419 ± 0.0204, P < .050.3611 ± 0.0547, P < .05
    IOD (at original magnification ×400)b
        NGF15.8494 ± 3.082516.6742 ± 1.7156
        EPO19.4382 ± 4.1861, P < .0522.4111 ± 4.3418, P < .01
    • a At 8 weeks after surgery, nerves treated with EPO had significantly larger myelin thickness and axon diameter compared with those in the NGF group, and there were statistically significant differences between the 2 groups.

    • b In addition, there were also statistically significant differences in MOD and IOD as well as myelinated axon counts between the 2 groups at the 2 time points.

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American Journal of Neuroradiology: 31 (3)
American Journal of Neuroradiology
Vol. 31, Issue 3
1 Mar 2010
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Cite this article
Z.-S. Yin, H. Zhang, W. Gao
Erythropoietin Promotes Functional Recovery and Enhances Nerve Regeneration after Peripheral Nerve Injury in Rats
American Journal of Neuroradiology Mar 2010, 31 (3) 509-515; DOI: 10.3174/ajnr.A1820

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Erythropoietin Promotes Functional Recovery and Enhances Nerve Regeneration after Peripheral Nerve Injury in Rats
Z.-S. Yin, H. Zhang, W. Gao
American Journal of Neuroradiology Mar 2010, 31 (3) 509-515; DOI: 10.3174/ajnr.A1820
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