DOI QR코드

DOI QR Code

Effect of task-specific training on Eph/ephrin expression after stroke

  • Choi, Dong-Hee (Department of Medical Science, Konkuk University School of Medicine) ;
  • Ahn, Jin-Hee (Department of Medical Science, Konkuk University School of Medicine) ;
  • Choi, In-Ae (Department of Medical Science, Konkuk University School of Medicine) ;
  • Kim, Ji-Hye (Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University) ;
  • Kim, Bo-Ram (Department of Rehabilitation Medicine, Konkuk University School of Medicine) ;
  • Lee, Jongmin (Department of Rehabilitation Medicine, Konkuk University School of Medicine)
  • Received : 2016.10.09
  • Accepted : 2016.10.17
  • Published : 2016.11.30

Abstract

Recent evidence indicates that the ephrin receptors and ephrin ligands (Eph/ephrin) expression modulate axonal reorganization and synaptic plasticity in stroke recovery. To investigate the effect of task-specific training (TST) on Eph/ephrin expression in the corticospinal tract (CST) after stroke, we compared Eph/ephrin expression in the peri-infarct cortex, pyramid, and spinal cord of a photothrombotic stroke model of rat brains treated with or without TST. The TST treatment showed significantly better recovery in the behavioral tests compared with no treatment. The significant upregulation of ephrin-A1 and ephrin-A5 observed in activated astrocytes of the CST at 2 weeks' post-stroke was decreased by TST. At 5 weeks, post-stroke, the elevated ephrin-A5 levels were decreased in the ipsilateral pyramid and spinal cord by TST. Glial fibrillary acidic protein was upregulated concomitantly with the altered ephrin expression after stroke, and the expression of these proteins was attenuated by TST. These data suggest that TST alters the expression of ephrin ligands in the CST after stroke.

Keywords

Eph/ephrin expression;Reactive astrocytes;Stroke;Stroke recovery;Task-specific training

Acknowledgement

Supported by : National Research Foundation of Korea(NRF), Korea Health Industry Development Institute (KHIDI)

References

  1. Wahl AS, Omlor W, Rubio JC et al (2014) Neuronal repair. Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke. Science 344, 1250-1255 https://doi.org/10.1126/science.1253050
  2. Murphy TH and Corbett D (2009) Plasticity during stroke recovery: from synapse to behaviour. Nat Rev Neurosci 10, 861-872 https://doi.org/10.1038/nrn2735
  3. Jang SH (2009) A review of the ipsilateral motor pathway as a recovery mechanism in patients with stroke. NeuroRehabilitation 24, 315-320
  4. Lee KH, Kim JH, Choi DH and Lee J (2013) Effect of task-specific training on functional recovery and corticospinal tract plasticity after stroke. Restor Neurol Neurosci 31, 773-785
  5. Liu Z, Li Y, Zhang X, Savant-Bhonsale S and Chopp M (2008) Contralesional axonal remodeling of the corticospinal system in adult rats after stroke and bone marrow stromal cell treatment. Stroke 39, 2571-2577 https://doi.org/10.1161/STROKEAHA.107.511659
  6. Carmichael ST (2006) Cellular and molecular mechanisms of neural repair after stroke: making waves. Ann Neurol 59, 735-742 https://doi.org/10.1002/ana.20845
  7. Lo EH (2008) A new penumbra: transitioning from injury into repair after stroke. Nat Med 14, 497-500 https://doi.org/10.1038/nm1735
  8. Benson MD, Romero MI, Lush ME, Lu QR, Henkemeyer M and Parada LF (2005) Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth. Proc Natl Acad Sci U S A 102, 10694-10699 https://doi.org/10.1073/pnas.0504021102
  9. Lemmens R, Jaspers T, Robberecht W and Thijs VN (2013) Modifying expression of EphA4 and its down-stream targets improves functional recovery after stroke. Hum Mol Genet 22, 2214-2220 https://doi.org/10.1093/hmg/ddt073
  10. Thundyil J, Manzanero S, Pavlovski D et al (2013) Evidence that the EphA2 receptor exacerbates ischemic brain injury. PLoS One 8, e53528 https://doi.org/10.1371/journal.pone.0053528
  11. Flanagan JG (2006) Neural map specification by gradients. Curr Opin Neurobiol 16, 59-66 https://doi.org/10.1016/j.conb.2006.01.010
  12. Yamaguchi Y and Pasquale EB (2004) Eph receptors in the adult brain. Curr Opin Neurobiol 14, 288-296 https://doi.org/10.1016/j.conb.2004.04.003
  13. Overman JJ, Clarkson AN, Wanner IB et al (2012) A role for ephrin-A5 in axonal sprouting, recovery, and activity-dependent plasticity after stroke. Proc Natl Acad Sci U S A 109, E2230-2239 https://doi.org/10.1073/pnas.1204386109
  14. Yang J, Luo X, Huang X, Ning Q, Xie M and Wang W (2014) Ephrin-A3 reverse signaling regulates hippocampal neuronal damage and astrocytic glutamate transport after transient global ischemia. J Neurochem 131, 383-394 https://doi.org/10.1111/jnc.12819
  15. Yokoyama N, Romero MI, Cowan CA et al (2001) Forward signaling mediated by ephrin-B3 prevents con-tralateral corticospinal axons from recrossing the spinal cord midline. Neuron 29, 85-97 https://doi.org/10.1016/S0896-6273(01)00182-9
  16. Kullander K, Croll SD, Zimmer M et al (2001) Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control. Genes Dev 15, 877-888 https://doi.org/10.1101/gad.868901
  17. Moses ZB, Abd-El-Barr MM and Chi JH (2015) Timing is everything in corticospinal tract recovery after stroke. Neurosurgery 76, N18-19 https://doi.org/10.1227/01.neu.0000462697.23265.f4
  18. Carmichael ST, Archibeque I, Luke L, Nolan T, Momiy J and Li S (2005) Growth-associated gene expression after stroke: evidence for a growth-promoting region in peri-infarct cortex. Exp Neurol 193, 291-311 https://doi.org/10.1016/j.expneurol.2005.01.004
  19. Goldshmit Y and Bourne J (2010) Upregulation of EphA4 on astrocytes potentially mediates astrocytic gliosis after a cortical lesion in the marmoset monkey. J Neurotrauma 27, 1321-1332 https://doi.org/10.1089/neu.2010.1294
  20. Bayona NA, Bitensky J, Salter K and Teasell R (2005) The role of task-specific training in rehabilitation therapies. Top Stroke Rehabil 12, 58-65
  21. Okabe N, Shiromoto T, Himi N et al (2016) Neural network remodeling underlying motor map reorganization induced by rehabilitative training after ischemic stroke. Neuroscience [Epub ahead of print]
  22. Wu LY, Yu XL and Feng LY (2015) Connexin 43 stabilizes astrocytes in a stroke-like milieu to facilitate neuronal recovery. Acta Pharmacol Sin 36, 928-938 https://doi.org/10.1038/aps.2015.39
  23. Choi JK, Park SY, Kim KH, Park SR, Lee SG and Choi BH (2014) GM-CSF reduces expression of chondroitin sulfate proteoglycan (CSPG) core proteins in TGF-beta-treated primary astrocytes. BMB Rep 47, 679-684 https://doi.org/10.5483/BMBRep.2014.47.12.018
  24. Feinklestein SP, Fisher M, Furland AJ et al (1999) Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke 30, 2752-2758 https://doi.org/10.1161/01.STR.30.12.2752
  25. Watson BD, Dietrich WD, Busto R, Wachtel MS and Ginsberg MD (1985) Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol 17, 497-504 https://doi.org/10.1002/ana.410170513
  26. Kim YJ, Kim JE, Choi HC, Song HK and Kang TC (2015) Cellular and regional specific changes in multidrug efflux transporter expression during recovery of vasogenic edema in the rat hippocampus and piriform cortex. BMB Rep 48, 348-353 https://doi.org/10.5483/BMBRep.2015.48.6.237

Cited by

  1. Axonal remodeling in the corticospinal tract after stroke: how does rehabilitative training modulate it? vol.12, pp.2, 2017, https://doi.org/10.4103/1673-5374.200792
  2. The evolving role of neuro-immune interaction in brain repair after cerebral ischemic stroke pp.17555930, 2018, https://doi.org/10.1111/cns.13077
  3. Roles of Eph/ephrin bidirectional signaling during injury and recovery of the central nervous system vol.13, pp.8, 2018, https://doi.org/10.4103/1673-5374.235217
  4. Effect of Inhibition of DNA Methylation Combined with Task-Specific Training on Chronic Stroke Recovery vol.19, pp.7, 2018, https://doi.org/10.3390/ijms19072019