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Combining Bone Marrow Stromal Cells with Green Tea Polyphenols Attenuates the Blood-Spinal Cord Barrier Permeability in Rats with Compression Spinal Cord Injury

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Abstract

This study was performed to investigate the effect of bone marrow stromal cells (BMSCs) combined with green tea polyphenols (GTPs) on the blood-spinal cord barrier (BSCB) permeability after spinal cord injury (SCI) in the rat model. In the model of SCI rats, we found that the water content and the BSCB permeability were decreased by BMSCs and GTPs treatment, and their combination had a synergistic effect. Further, the motor function of rats was also greatly improved by BMSCs and GTPs administration. After treated by the combination of BMSCs and GTPs, SCI rats showed the up-regulated expression of tight junction (TJ) associated proteins claudin-5, occludin and ZO-1 by Western blot, which was more remarkable than that in the single treatment. The increased expression levels of claudin-5, occludin, and ZO-1 were the most obvious in the spinal cord microvessels using immunohistochemistry assay. This led to the conclusion that the combination of BMSCs and GTPs could decrease the BSCB permeability by up-regulating protein expression levels of claudin-5, occludin, and ZO-1. In addition, after BMSCs and GTPs administration, the results of Western blot and enzyme-linked immunosorbent assay (ELISA) revealed a significant decrease in protein expression level and the activation of nuclear factor-кB (NF-кB) p65. Our results indicated that combination of BMSCs and GTPs could improve motor function after SCI, which might be correlated with improvements in BSCB integrity, and that NF-кB might be involved in the modulating process.

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References

  • Aslam M, Ahmad N, Srivastava R et al (2012) TNF-alpha induced NFκB signaling and p65 (RelA) overexpression repress Cldn5 promoter in mouse brain endothelial cells. Cytokine 57(2):269–275

    Article  CAS  PubMed  Google Scholar 

  • Bartanusz V, Jezova D, Alajajian B et al (2011) The blood-spinal cord barrier: morphology and clinical implications. Ann Neurol 70(2):194–206

    Article  PubMed  Google Scholar 

  • Basso DM, Beattie MS, Bresnahan JC (1995) A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 12:1–21

    Article  CAS  PubMed  Google Scholar 

  • Beattie MS (2004) Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol Med 10:580–583

    Article  CAS  PubMed  Google Scholar 

  • Bilgen M, Dogan B, Narayana PA (2002) In vivo assessment of blood-spinal cord barrier permeability: serial dynamic contrast enhanced MRI of spinal cord injury. Magn Reson Imaging 20(4):337–341

    Article  PubMed  Google Scholar 

  • Borlongan CV, Lind JG, Dillon-Carter O et al (2004) Bone marrow grafts restore cerebral blood flow and blood brain barrier in stroke rats. Brain Res 1010(1–2):108–116

    Article  CAS  PubMed  Google Scholar 

  • Burek M, Förster CY (2009) Cloning and characterization of the murine claudin-5 promoter. Mol Cell Endocrinol 298(1–2):19–24

    Article  CAS  PubMed  Google Scholar 

  • Cao C, Zou J, Liu X et al (2014) Ebraheim N.Bone marrow mesenchymal stem cells slow intervertebral disc degeneration through the NF-κB pathway. Spine J S1529–9430(14):01767–7

    Google Scholar 

  • Cohen DM, Patel CB, Ahobila-Vajjula P et al (2009) Blood-spinal cord barrier permeability in experimental spinal cord injury: dynamic contrast-enhanced MRI. NMR Biomed 22(3):332–341

    Article  PubMed Central  PubMed  Google Scholar 

  • Dasari VR, Veeravalli KK, Dinh DH (2014) Mesenchymal stem cells in the treatment of spinal cord injuries: a review. World J Stem Cells 6(2):120–133

    Article  PubMed Central  PubMed  Google Scholar 

  • Fang B, Wang H, Sun XJ et al (2013) Intrathecal transplantation of bone marrow stromal cells attenuates blood-spinal cord barrier disruption induced by spinal cord ischemia-reperfusion injury in rabbits. J Vasc Surg 58(4):1043–1052

    Article  PubMed  Google Scholar 

  • Figley SA, Khosravi R, Legasto JM et al (2014) Characterization of vascular disruption and blood-spinal cord barrierpermeability following traumatic spinal cord injury. J Neurotrauma 31:541–552

    Article  PubMed Central  PubMed  Google Scholar 

  • Frei B, Higdon JV (2003) Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. J Nutr 133:3275S–3284S

    CAS  PubMed  Google Scholar 

  • He F, Peng J, Deng XL et al (2012) Mechanisms of tumor necrosis factor-alpha-induced leaks in intestine epithelial barrier. Cytokine 59:264–272

    Article  CAS  PubMed  Google Scholar 

  • Hügel HM, Jackson N (2012) Redox chemistry of green tea polyphenols: therapeutic benefits in neurodegenerative diseases. Mini Rev Med Chem 12(5):380–387

    Article  PubMed  Google Scholar 

  • Joshi M, Fehlings MG (2002) Development and characterization of a novel, graded model of clip compressive spinal cord injury in the mouse: Part 1. Clip design, behavioral outcomes, and histopathology. J Neurotrauma 19:175–190

    Article  PubMed  Google Scholar 

  • Kitada M (2012) Mesenchymal cell populations: development of the induction systems for Schwann cells and neuronal cells and finding the unique stem cell population. Anat Sci Int 87(1):24–44

    Article  CAS  PubMed  Google Scholar 

  • Lee JY, Choi HY, Ahn HJ et al (2014) Matrix metalloproteinase-3 promotes early blood-spinal cord barrier disruption and hemorrhage and impairs long-term neurological recovery after spinal cord injury. Am J Pathol 184(11):2985–3000

    Article  CAS  PubMed  Google Scholar 

  • Li XQ, Wang J, Fang B et al (2014) Intrathecal antagonism of microglial TLR4 reduces inflammatory damage to blood-spinal cord barrier following ischemia/reperfusion injury in rats. Mol Brain 7:28

    Article  PubMed Central  PubMed  Google Scholar 

  • Liebner S, Czupalla CJ, Wolburg H (2011) Current concepts of blood–brain barrier development. Int J Dev Biol 55(4–5):467–476

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Wang Z, Wang P et al (2013) Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling. BMC Complement Altern Med 13:187

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu Y, Tang G, Li Y et al (2014) Metformin attenuates blood–brain barrier disruption in mice following middle cerebral artery occlusion. J Neuroinflammation 11:177

    Article  PubMed Central  PubMed  Google Scholar 

  • Luissint AC, Artus C, Glacial F et al (2012) Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation. Fluid Barriers CNS 9:23

    Article  Google Scholar 

  • Mandel SA, Amit T, Weinreb O et al (2011) Understanding the broad-spectrum neuroprotective action profile of green tea polyphenols in aging and neurodegenerative diseases. J Alzheimers Dis 25(2):187–208

    CAS  PubMed  Google Scholar 

  • Menon PK, Muresanu DF, Sharma A et al (2012) Cerebrolysin, a mixture of neurotrophic factors induces marked neuroprotection inspinal cord injury following intoxication of engineered nanoparticles from metals. CNS Neurol Disord Drug Target 11(1):40–49

    Article  CAS  Google Scholar 

  • Mitsuhara T, Takeda M, Yamaguchi S et al (2013) Simulated microgravity facilitates cell migration and neuroprotection after bone marrow stromal cell transplantation in spinal cord injury. Stem Cell Res Ther 4(2):35

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Oz HS, Ebersole JL (2010) Green tea polyphenols mediated apoptosis in intestinal epithelial cells by a fadd-dependent pathway. J Cancer Ther 1(3):105–113

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sharma HS (2011) Early microvascular reactions and blood-spinal cord barrier disruption are instrumental in pathophysiology of spinal cord injury and repair: novel therapeutic strategies including nanowired drug delivery to enhance neuroprotection. J Neural Transm 118(1):155–176

    Article  CAS  PubMed  Google Scholar 

  • Tian ZR, Sharma A, Nozari A et al (2012) Nanowired drug delivery to enhance neuroprotection in spinal cord injury. CNS Neurol Disord Drug Target 11(1):86–95

    Article  CAS  Google Scholar 

  • Tohill M, Mantovani C, Wiberg M et al (2004) Rat bone marrowmesenchymal stem cells express glial markers and stimulate nerve regeneration. Neurosci Lett 362:200–203

    Article  CAS  PubMed  Google Scholar 

  • Vignes M, Maurice T, Lante F (2006) Anxiolytic properties of green tea polyphenol (−)-epigallocatechin gallate (EGCG). Brain Res 1110:102–115

    Article  CAS  PubMed  Google Scholar 

  • Yu DS, Liu LB, Zhi XD et al (2011) Increased vascular endothelial growth factor (VEGF) expression in rats with spinal cord injury by transplantation of bone marrow stromal cells. Afr J Biotechnol 10(20):4249–4255

    CAS  Google Scholar 

  • Zacharek A, Chen J, Cui X et al (2007) Angiopoietin1/Tie2 and VEGF/Flk1 induced by MSC treatment amplifies angiogenesis and vascular stabilization after stroke. J Cereb Blood Flow Metab 27(10):1684–1691

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang S, Liu Y, Zhao Z et al (2010) Effects of green tea polyphenols on caveolin-1 of microvessel fragments in rats with cerebral ischemia. Neurol Res 32(9):963–970

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Natural Science Foundation of China (Nos. 81171799, 81272074, and 81471853), Doctoral Scientific Research Starting Foundation of Liaoning Province (No. 20121096), Program for Liaoning Excellent Talents in University (No. LR2013091), Scientific Research Starting Foundation for PHD and Returned Overseas Teacher of Liaoning Medical University (No. Y2012B011), and Special Funds for Clinical Medicine Construction of the Principal’s Fund of the Liaoning Medical University (No. XZJJ20130241).

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The authors declare that there are no conflicts to disclose.

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Correspondence to Xi-fan Mei.

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Yu, Ds., Liu, Lb., Cao, Y. et al. Combining Bone Marrow Stromal Cells with Green Tea Polyphenols Attenuates the Blood-Spinal Cord Barrier Permeability in Rats with Compression Spinal Cord Injury. J Mol Neurosci 56, 388–396 (2015). https://doi.org/10.1007/s12031-015-0564-z

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  • DOI: https://doi.org/10.1007/s12031-015-0564-z

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