Human recombinant erythropoietin improves motor function in rats with spinal cord compression-induced cervical myelopathy.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
10
03
2019
accepted:
12
11
2019
entrez:
11
12
2019
pubmed:
11
12
2019
medline:
25
3
2020
Statut:
epublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 31821342
doi: 10.1371/journal.pone.0214351
pii: PONE-D-19-06960
pmc: PMC6903714
doi:
Substances chimiques
EPO protein, human
0
Recombinant Proteins
0
Erythropoietin
11096-26-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0214351Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Spine (Phila Pa 1976). 2011 Jun;36(13):1006-9
pubmed: 21192287
Spine (Phila Pa 1976). 2016 Dec 1;41(23):E1380-E1387
pubmed: 27120060
Int J Neurosci. 2015;125(9):693-702
pubmed: 25226558
Pediatr Res. 2007 Jun;61(6):671-5
pubmed: 17426655
Am J Pathol. 1992 Apr;140(4):787-94
pubmed: 1373270
J Chromatogr B Biomed Appl. 1996 Dec 6;687(1):189-99
pubmed: 9001965
J Comp Neurol. 1989 Nov 15;289(3):375-85
pubmed: 2808773
Am J Med Sci. 2017 Jan;353(1):76-81
pubmed: 28104107
J Mol Neurosci. 2013 Feb;49(2):369-79
pubmed: 23001813
J Clin Neurosci. 2007 Apr;14(4):364-8
pubmed: 17236773
Clin Spine Surg. 2017 Nov;30(9):383-388
pubmed: 28338491
J Trauma Acute Care Surg. 2014 May;76(5):1228-34
pubmed: 24747453
Genet Mol Res. 2015 Dec 22;14(4):17799-808
pubmed: 26782425
Panminerva Med. 2008 Jun;50(2):185-92
pubmed: 18607342
Sci Transl Med. 2015 Dec 2;7(316):316ra194
pubmed: 26631633
Zhonghua Bing Li Xue Za Zhi. 2015 May;44(5):323-8
pubmed: 26178214
J Vet Med Sci. 1996 Dec;58(12):1219-21
pubmed: 8996705
Ann Neurol. 2004 Apr;55(4):503-11
pubmed: 15048889
Onkologie. 2002 Feb;25(1):32-9
pubmed: 11893881
Open Orthop J. 2011;5:335-42
pubmed: 21966338
Spine (Phila Pa 1976). 2011 May 15;36(11):865-9
pubmed: 21192291
Lancet. 1986 Nov 22;2(8517):1175-8
pubmed: 2877323
Microvasc Res. 2002 Sep;64(2):326-33
pubmed: 12204656
Pharmacol Ther. 2010 Dec;128(3):445-59
pubmed: 20732352
Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16379-84
pubmed: 16260722
Spine (Phila Pa 1976). 2013 Oct 15;38(22 Suppl 1):S21-36
pubmed: 23963004
J Neurosurg Spine. 2014 Jan;20(1):93-101
pubmed: 24206033
J Biol Chem. 1994 Jul 29;269(30):19488-93
pubmed: 8034718
News Physiol Sci. 2000 Oct;15:225-229
pubmed: 11390915
Turk Neurosurg. 2015;25(4):552-8
pubmed: 26242331
J Neurosurg. 2014 Sep;121(3):653-64
pubmed: 25036201
J Neurosurg Spine. 2009 Aug;11(2):112-8
pubmed: 19769490
Transfusion. 2001 Feb;41(2):184-9
pubmed: 11239220
Neurosurg Rev. 2004 Apr;27(2):113-20
pubmed: 12920606
Biomed Pharmacother. 2017 Mar;87:332-341
pubmed: 28064106
Prog Brain Res. 1964;11:58-92
pubmed: 14300483
Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10526-31
pubmed: 10984541
J Neuroimaging. 2015 Jul-Aug;25(4):582-9
pubmed: 25510176
Blood Rev. 2016 Nov;30(6):453-459
pubmed: 27341755
Exp Neurol. 2016 Feb;276:59-71
pubmed: 26394202
Clin Neurol Neurosurg. 2007 Oct;109(8):639-44
pubmed: 17624659
J Neurobiol. 1992 Jul;23(5):507-20
pubmed: 1431834
Spine (Phila Pa 1976). 2013 Oct 15;38(22 Suppl 1):S68-75
pubmed: 23962993
J Bone Joint Surg Am. 2013 Sep 18;95(18):1651-8
pubmed: 24048552
Pediatr Res. 1999 Nov;46(5):543-7
pubmed: 10541316
Neurol Sci. 2015 Sep;36(9):1567-74
pubmed: 25820146
Neurosci Lett. 2017 May 22;650:12-17
pubmed: 28359933
Semin Thromb Hemost. 2010 Jul;36(5):537-49
pubmed: 20632251
Eur Spine J. 2003 Oct;12 Suppl 2:S86-9
pubmed: 12961079
Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9450-5
pubmed: 12082184
Eur J Pediatr. 1997 Apr;156(4):305-10
pubmed: 9128817
Acta Neuropathol Commun. 2016 Aug 23;4(1):89
pubmed: 27552807
Neurosci Lett. 2011 Feb 18;490(1):57-62
pubmed: 21167907
J Neuroinflammation. 2018 Aug 6;15(1):222
pubmed: 30081922
Neurobehav Toxicol. 1979 Fall;1(3):233-6
pubmed: 551317