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PMID- 29489692
DCOM- 20180307
LR  - 20180307
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Linking)
VI  - 97
IP  - 9
DP  - 2018 Mar
TI  - Therapeutic time window for the effects of erythropoietin on astrogliosis and
      neurite outgrowth in an in vitro model of spinal cord injury.
PG  - e9913
LID - 10.1097/MD.0000000000009913 [doi]
AB  - BACKGROUND: The objective of this study was to investigate the underlying
      molecular mechanisms and the therapeutic time window for preventing astrogliosis 
      with erythropoietin (EPO) treatment after in vitro modeled spinal cord injury
      (SCI). METHODS: Cultured rat spinal cord astrocytes were treated with kainate and
      scratching to generate an in vitro model of SCI. EPO (100U/mL or 300U/mL) was
      added immediately or 2, 4, or 8 hours after injury. Some cultures were also
      treated with AG490, an inhibitor of the EPO-EPO receptor (EpoR) pathway mediator 
      Janus kinase 2 (JAK2). To evaluate neurite extension, rat embryonic spinal cord
      neurons were seeded onto astrocyte cultures and treated with EPO immediately
      after injury in the presence or absence of anti-EpoR antibody. RESULTS: EPO
      treatment at up to 8 hours after injury reduced the expression of axonal growth
      inhibiting molecules (glial fibrillary acidic protein, vimentin, and chondroitin 
      sulfate proteoglycan), cytoskeletal regulatory proteins (Rho-associated protein
      kinase and ephephrin A4), and proinflammatory cytokines (tumor necrosis
      factor-alpha, transforming growth factor-beta, and phosphorylated-Smad3) in a
      dosedependent manner (P < .001). Most effects peaked with EPO treatment 2-4hours 
      after injury. Additionally, EPO treatment up to 4 hours after injury promoted
      expression of the EpoR (>2-fold) and JAK2 (>3-fold) in a dose-dependent manner (P
      < .001), whereas co-treatment with AG490 precluded these effects (P < .001). EPO 
      treatment up to 4hours after injury also enhanced axonal b-III
      tubulin-immunoreactivity (>12-fold), and this effect was precluded by
      co-treatment with an anti-EpoR antibody (P < .001). CONCLUSIONS: EPO treatment
      within 8 hours after injury reduced astrogliosis, and EPO treatment within 4
      hours promoted neurite outgrowth. EPO therapy immediately after spinal cord
      injury may regulate glia to generate an environment permissive of axonal
FAU - Hong, Hea Nam
AU  - Hong HN
AD  - Department of Anatomy.
FAU - Shim, Ju Hee
AU  - Shim JH
AD  - Department of Anatomy.
FAU - Won, You Jin
AU  - Won YJ
AD  - Department of Anatomy.
FAU - Yoo, Jong Yoon
AU  - Yoo JY
AD  - Department of Rehabilitation Medicine, Asan Medical Center.
FAU - Hwang, Chang Ho
AU  - Hwang CH
AD  - Department of Physical Medicine and Rehabilitation, Ulsan University Hospital,
      University of Ulsan College of Medicine, Republic of Korea.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 11096-26-7 (Erythropoietin)
SB  - IM
MH  - Animals
MH  - Astrocytes
MH  - Axons/drug effects
MH  - Cells, Cultured
MH  - Drug Administration Schedule
MH  - Erythropoietin/*administration & dosage
MH  - Gliosis/*drug therapy
MH  - Neuronal Outgrowth/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spinal Cord Injuries/*drug therapy
MH  - *Time-to-Treatment
EDAT- 2018/03/01 06:00
MHDA- 2018/03/08 06:00
CRDT- 2018/03/01 06:00
PHST- 2018/03/01 06:00 [entrez]
PHST- 2018/03/01 06:00 [pubmed]
PHST- 2018/03/08 06:00 [medline]
AID - 10.1097/MD.0000000000009913 [doi]
AID - 00005792-201803020-00053 [pii]
PST - ppublish
SO  - Medicine (Baltimore). 2018 Mar;97(9):e9913. doi: 10.1097/MD.0000000000009913.