Anti‑inflammatory compound curcumin and mesenchymal stem cells in the treatment of spinal cord injury in rats

• Autorzy: Ruzicka J. , Urdzikova L.M. , Kloudova A. , Amin A.G. , Vallova J. , Kubinova S. , Schmidt M.H. , Jhanwar-Uniyal M. , Jendelova P.
• Języki publikacji: EN

Abstrakty

EN

Spinal cord injury leads to a robust inflammatory response that is an unfavorable environment for stem cell implantation. In this study, we evaluated the effect of combined therapy of curcumin and mesenchymal stem cells (MSC) on behavioral recovery and tissue sparing, glial scar formation, axonal sprouting and inflammatory responses in a rat experimental model of spinal cord injury (SCI). Balloon‑induced compression lesion was performed at thoracic (Th8‑9) spinal level. Out of the four groups studied, two groups received curcumin on the surface of the spinal cord immediately after SCI and then once a week for 3 weeks together with an intraperitoneal daily curcumin injection for 28 days. The other two groups received saline. Seven days after SCI, human MSC were intrathecally implanted in one curcumin and one saline group. Both curcumin and curcumin combined with MSC treatment improved locomotor ability in comparison to the saline treated animals. The combined treatment group showed additional improvement in advanced locomotor performance. The combined therapy facilitated axonal sprouting, and modulated expression of pro‑regenerative factors and inflammatory responses, when compared to saline and single treatments. These results demonstrate that preconditioning with curcumin, prior to the MSC implantation could have a synergic effect in the treatment of experimental SCI

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2018
• Tom: 78
• Numer: 4
• Opis fizyczny: p.358-374,fig.,ref.

Twórcy

autor

Ruzicka J.

• Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic

autor

Urdzikova L.M.

• Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic

autor

Kloudova A.

• Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic

autor

Amin A.G.

• Department of Neuroscience, Second Faculty of Medicine, Charles University, Prague, Czech Republic

autor

Vallova J.

• Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic

autor

Kubinova S.

• Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic

autor

Schmidt M.H.

• New York Medical College, Westchester Medical Center, Valhalla New York, USA

autor

Jhanwar-Uniyal M.

• New York Medical College, Westchester Medical Center, Valhalla New York, USA

autor

Jendelova P.

• Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Bibliografia

• Anthony DC, Couch Y (2014) The systemic response to CNS injury. Exp Neurol 258: 105–111.
• 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.
• Bretzner F, Liu J, Currie E, Roskams AJ, Tetzlaff W (2008) Undesired effects of a combinatorial treatment for spinal cord injury ‑ transplantation of olfactory ensheathing cells and BDNF infusion to the red nucleus. Eur J Neurosci 28: 1795–1807.
• Callera F, do Nascimento RX (2006) Delivery of autologous bone marrow precursor cells into the spinal cord via lumbar puncture technique in patients with spinal cord injury: a preliminary safety study. Exp Hematol 34: 130–131.
• Carstens E, Ansley D (1993) Hindlimb flexion withdrawal evoked by noxious heat in conscious rats: magnitude measurement of stimulus‑response function, suppression by morphine and habituation. J Neurophysiol 70: 621–629.
• Carter RJ, Morton J, Dunnett SB (2001) Motor coordination and balance in rodents. Curr Protoc Neurosci 8: 12.
• Chen JJ, Dai L, Zhao LX, Zhu X, Cao S, Gao YJ (2015) Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal neuroinflammation in rat model of monoarthritis. Sci Rep 5: 10278.
• Cocks G, Romanyuk N, Amemori T, Jendelova P, Forostyak O, Jeffries AR, Perfect L, Thuret S, Dayanithi G, Sykova E, Price J (2013) Conditionally immortalized stem cell lines from human spinal cord retain regional identity and generate functional V2a interneurons and motorneurons. Stem Cell Res Ther 4: 69.
• Daverey A, Agrawal SK (2016) Curcumin alleviates oxidative stress and mitochondrial dysfunction in astrocytes. Neuroscience 333: 92–103.
• Dong HJ, Shang CZ, Peng DW, Xu J, Xu PX, Zhan L, Wang P (2014) Curcumin attenuates ischemia‑like injury induced IL‑1beta elevation in brain microvascular endothelial cells via inhibiting MAPK pathways and nuclear factor‑kappaB activation. Neurol Sci 35: 1387–1392.
• Forostyak S, Homola A, Turnovcova K, Svitil P, Jendelova P, Sykova E (2014) Intrathecal delivery of mesenchymal stromal cells protects the structure of altered perineuronal nets in SOD1 rats and amends the course of ALS. Stem Cells 32: 3163–3172.
• Forostyak S, Jendelova P, Sykova E (2013) The role of mesenchymal stromal cells in spinal cord injury, regenerative medicine and possible clinical applications. Biochimie 95: 2257–2270.
• Francos‑Quijorna I, Amo‑Aparicio J, Martinez‑Muriana A, Lopez‑Vales R (2016) IL‑4 drives microglia and macrophages toward a phenotype conducive for tissue repair and functional recovery after spinal cord injury. Glia 64: 2079–2092.
• Gaudet AD, Fonken LK (2018) Glial cells shape pathology and repair after spinal cord injury. Neurotherapeutics 15: 554–577.
• Geffner LF, Santacruz P, Izurieta M, Flor L, Maldonado B, Auad AH, Montenegro X, Gonzalez R, Silva F (2008) Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: comprehensive case studies. Cell Transplant 17: 1277–1293.
• Gokce EC, Kahveci R, Gokce A, Sargon MF, Kisa U, Aksoy N, Cemil B, Erdogan B (2016) Curcumin attenuates inflammation, oxidative stress, and ultrastructural damage induced by spinal cord ischemia‑reperfusion injury in rats. J Stroke Cerebrovasc Dis 25: 1196–1207.
• Goldstein LB (1997) Effects of bilateral and unilateral locus coeruleus lesions on beam‑walking recovery after subsequent unilateral sensorimotor cortex suction‑ablation in the rat. Restor Neurol Neurosci 11: 55–63.
• Hawryluk GW, Mothe A, Wang J, Wang S, Tator C, Fehlings MG (2012) An in vivo characterization of trophic factor production following neural precursor cell or bone marrow stromal cell transplantation for spinal cord injury. Stem Cells Dev 21: 2222–2238.
• Hidaka H, Ishiko T, Furuhashi T, Kamohara H, Suzuki S, Miyazaki M, Ikeda O, Mita S, Setoguchi T, Ogawa M (2002) Curcumin inhibits interleukin 8 production and enhances interleukin 8 receptor expression on the cell surface: impact on human pancreatic carcinoma cell growth by autocrine regulation. Cancer 95: 1206–1214.
• Jain SK, Rains J, Croad J, Larson B, Jones K (2009) Curcumin supplementation lowers TNF‑alpha, IL‑6, IL‑8, and MCP‑1 secretion in high glucose‑treated cultured monocytes and blood levels of TNF‑alpha, IL‑6, MCP‑1, glucose, and glycosylated hemoglobin in diabetic rats. Antioxid Redox Signal 11: 241–249.
• Jiang H, Tian X, Guo Y, Duan W, Bu H, Li C (2011) Activation of nuclear factor erythroid 2‑related factor 2 cytoprotective signaling by curcumin protect primary spinal cord astrocytes against oxidative toxicity. Biol Pharm Bull 34: 1194–1197.
• Kocsis JD, Honmou O (2012) Bone marrow stem cells in experimental stroke. Prog Brain Res 201: 79–98.
• Kuroda S, Shichinohe H, Houkin K, Iwasaki Y (2011) Autologous bone marrow stromal cell transplantation for central nervous system disorders – recent progress and perspective for clinical application. J Stem Cells Regen Med 7: 2–13.
• LaPlaca MC, Simon CM, Prado GR, Cullen DK (2007) CNS injury biomechanics and experimental models. Prog Brain Res 161: 13–26.
• Lee JY, Shin TJ, Choi JM, Seo KS, Kim HJ, Yoon TG, Lee YS, Han H, Chung HJ, Oh Y, Jung SJ, Shin KJ (2013) Antinociceptive curcuminoid, KMS4034, effects on inflammatory and neuropathic pain likely via modulating TRPV1 in mice. Br J Anaesth 111: 667–672.
• Lee SI, Jeong SR, Kang YM, Han DH, Jin BK, Namgung U, Kim BG (2010) Endogenous expression of interleukin‑4 regulates macrophage activa tion and confines cavity formation after traumatic spinal cord injury. J Neurosci Res 88: 2409–2419.
• Lin MS, Sun YY, Chiu WT, Hung CC, Chang CY, Shie FS, Tsai SH, Lin JW, Hung KS, Lee YH (2011) Curcumin attenuates the expression and secretion of RANTES after spinal cord injury in vivo and lipopolysaccharide‑induced astrocyte reactivation in vitro. J Neurotrauma 28: 1259–1269.
• Liu W, Wang Y, Gong F, Rong Y, Luo Y, Tang P, Zhou Z, Xu T, Jiang T, Yang S, Yin G, Chen J, Fan J, Cai  W (2018) Exosomes derived from bone mesenchymal stem cells repair traumatic spinal cord injury by suppressing the activation of A1 neurotoxic reactive astrocytes. J Neurotrauma doi: 10.1089/neu.2018.5835. [Epub ahead of print]
• Lu Z, Shen Y, Wang T, Cui M, Wang Z, Zhao H, Dong Q (2014) Curcumin promotes neurite outgrowth via reggie‑1/flotillin‑2 in cortical neurons. Neurosci Lett 559: 7–12.
• Machova Urdzikova  L, Karova K, Ruzicka J, Kloudova A, Shannon C, Dubisova J, Murali R, Kubinova S, Sykova E, Jhanwar‑Uniyal M, Jendelova P (2015) The anti‑inflammatory compound curcumin enhances locomotor and sensory recovery after spinal cord injury in rats by immunomodulation. Int J Mol Sci 17: pii E49.
• Morita T, Sasaki  M, Kataoka‑Sasaki Y, Nakazaki  M, Nagahama H, Oka S, Oshigiri T, Takebayashi T, Yamashita T, Kocsis JD, Honmou O (2016) Intravenous infusion of mesenchymal stem cells promotes functional recovery in a model of chronic spinal cord injury. Neuroscience 335: 221–231.
• Mukhamedshina YO, Akhmetzyanova ER, Kostennikov AA, Zakirova EY, Galieva LR, Garanina EE, Rogozin AA, Kiassov AP, Rizvanov AA (2018) Adipose‑derived mesenchymal stem cell application combined with fibrin matrix promotes structural and functional recovery following spinal cord injury in rats. Front Pharmacol 9: 343.
• Naeimi R, Safarpour F, Hashemian M, Tashakorian H, Ahmadian SR, Ashrafpour  M, Ghasemi‑Kasman  M (2018) Curcumin‑loaded nanoparticles ameliorate glial activation and improve myelin repair in lyolecithin‑induced focal demyelination model of rat corpus callosum. Neurosci Lett 674: 1–10.
• Nakajima H, Uchida K, Guerrero AR, Watanabe S, Sugita D, Takeura N, Yoshida A, Long G, Wright KT, Johnson WE, Baba H (2012) Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury. J Neurotrauma 29: 1614–1625.
• Ni H, Jin W, Zhu T, Wang J, Yuan B, Jiang J, Liang W, Ma Z (2015) Curcumin modulates TLR4/NF‑kappaB inflammatory signaling pathway following traumatic spinal cord injury in rats. J Spinal Cord Med 38: 199–206.
• Ormond DR, Peng H, Zeman R, Das K, Murali R, Jhanwar‑Uniyal M (2012) Recovery from spinal cord injury using naturally occurring antiinflammatory compound curcumin: laboratory investigation. J Neurosurg Spine 16: 497–503.
• Park DY, Mayle RE, Smith RL, Corcoran‑Schwartz I, Kharazi AI, Cheng I (2013) Combined transplantation of human neuronal and mesenchymal stem cells following spinal cord injury. Global Spine J 3: 1–6.
• Park HJ, Shin JY, Kim HN, Oh SH, Song SK, Lee PH (2015) Mesenchymal stem cells stabilize the blood‑brain barrier through regulation of astrocytes. Stem Cell Res Ther 6: 187. Pfaffl MW (2001) A new mathematical model for relative quantification in real‑time RT‑PCR. Nucleic Acids Res 29: e45.
• Requejo‑Aguilar R, Alastrue‑Agudo A, Cases‑Villar  M, Lopez‑Mocholi  E, England R, Vicent MJ, Moreno‑Manzano  V (2017) Combined polymer‑curcumin conjugate and ependymal progenitor/stem cell treatment enhances spinal cord injury functional recovery. Biomaterials 113: 18–30.
• Ritfeld GJ, Nandoe Tewarie RD, Vajn K, Rahiem ST, Hurtado A, Wendell DF, Roos RA, Oudega M (2012) Bone marrow stromal cell‑mediated tissue sparing enhances functional repair after spinal cord contusion in adult rats. Cell Transplant 21: 1561–1575.
• Ruzicka J, Kulijewicz‑Nawrot M, Rodrigez‑Arellano JJ, Jendelova P, Sykova E (2016) Mesenchymal stem cells preserve working memory in the 3xTg‑AD mouse model of Alzheimer’s disease. Int J Mol Sci 17: 152.
• Ruzicka J, Urdzikova LM, Svobodova B, Amin AG, Karova K, Dubisova J, Zaviskova K, Kubinova S, Schmidt  M, Jhanwar‑Uniyal  M, Jendelova P (2018) Does combined therapy of curcumin and epigallocatechin gallate have a synergistic neuroprotective effect against spinal cord injury? Neural Regen Res 13: 119–127.
• Sanivarapu R, Vallabhaneni V, Verma V (2016) The potential of curcumin in treatment of spinal cord injury. Neurol Res Int ID: 9468193.
• Sanli AM, Turkoglu E, Serbes G, Sargon MF, Besalti O, Kilinc K, Irak A, Sekerci  Z (2012) Effect of curcumin on lipid peroxidation, early ultrastructural findings and neurological recovery after experimental spinal cord contusion injury in rats. Turk Neurosurg 22: 189–195.
• Satake K, Lou J, Lenke LG (2004) Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue. Spine 29: 1971–1979.
• Seyedzadeh MH, Safari Z, Zare A, Gholizadeh Navashenaq J, Razavi SA, Kardar GA, Khorramizadeh MR (2014) Study of curcumin immunomodulatory effects on reactive astrocyte cell function. Int Immunopharmacol 22: 230–235.
• Tegenge MA, Rajbhandari L, Shrestha S, Mithal A, Hosmane S, Venkatesan A (2014) Curcumin protects axons from degeneration in the setting of local neuroinflammation. Exp Neurol 253: 102–110.
• Teixeira FG, Carvalho MM, Sousa N, Salgado AJ (2013) Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration? Cell Mol Life Sci 70: 3871–3882.
• Tsumuraya T, Ohtaki H, Song D, Sato A, Watanabe J, Hiraizumi Y, Nakamachi T, Xu Z, Dohi K, Hashimoto H, Atsumi T, Shioda S (2015) Human mesenchymal stem/stromal cells suppress spinal inflammation in mice with contribution of pituitary adenylate cyclase‑activating polypeptide (PACAP). J Neuroinflammation 12: 35.
• Urdzikova L, Jendelova P, Glogarova K, Burian M, Hajek M, Sykova E (2006) Transplantation of bone marrow stem cells as well as mobilization by granulocyte‑colony stimulating factor promotes recovery after spinal cord injury in rats. J Neurotrauma 23: 1379–1391.
• Urdzikova LM, Ruzicka J, LaBagnara M, Karova K, Kubinova S, Jirakova K, Murali R, Sykova E, Jhanwar‑Uniyal M, Jendelova P (2014) Human mesenchymal stem cells modulate inflammatory cytokines after spinal cord injury in rat. Int J Mol Sci 15: 11275–11293.
• Vanicky I, Urdzikova L, Saganova K, Cizkova D, Galik J (2001) A simple and reproducible model of spinal cord injury induced by epidural balloon inflation in the rat. J Neurotrauma 18: 1399–1407.
• Wang L, Wei FX, Cen JS, Ping SN, Li ZQ, Chen NN, Cui SB, Wan Y, Liu SY (2014a) Early administration of tumor necrosis factor‑alpha antagonist promotes survival of transplanted neural stem cells and axon myelination after spinal cord injury in rats. Brain Res 1575: 87–100.
• Wang Q, Sun AY, Simonyi A, Jensen MD, Shelat PB, Rottinghaus GE, MacDonald RS, Miller DK, Lubahn DE, Weisman GA, Sun GY (2005) Neuroprotective mechanisms of curcumin against cerebral ischemia‑induced neuronal apoptosis and behavioral deficits. J  Neurosci Res 82: 138–148.
• Wang YF, Zu JN, Li J, Chen C, Xi CY, Yan JL (2014b) Curcumin promotes the spinal cord repair via inhibition of glial scar formation and inflammation. Neurosci Lett 560: 51–56.
• Yang G, Tang WY (2017) Resistance of interleukin‑6 to the extracellular inhibitory environment promotes axonal regeneration and functional recovery following spinal cord injury. International journal of molecular medicine 39: 437–445.
• Yuan J, Zou M, Xiang X, Zhu H, Chu W, Liu W, Chen F, Lin J (2015) Curcumin improves neural function after spinal cord injury by the joint inhibition of the intracellular and extracellular components of glial scar. J Surg Res 195: 235–245.
• Zhang N, Wei G, Ye J, Yang L, Hong Y, Liu G, Zhong H, Cai X (2017) Effect of curcumin on acute spinal cord injury in mice via inhibition of inflammation and TAK1 pathway. Pharmacol Rep 69: 1001–1006.
• Zhao Z, Li X, Li Q (2017) Curcumin accelerates the repair of sciatic nerve injury in rats through reducing Schwann cells apoptosis and promoting myelinization. Biomed Pharmacother 92: 1103–1110.
• Zhu HT, Bian C, Yuan JC, Chu WH, Xiang X, Chen F, Wang CS, Feng H, Lin JK (2014) Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF‑kappaB signaling pathway in experimental traumatic brain injury. J Neuroinflammation 11: 59.
• Zu J, Wang Y, Xu G, Zhuang J, Gong H, Yan J (2014) Curcumin improves the recovery of motor function and reduces spinal cord edema in a rat acute spinal cord injury model by inhibiting the JAK/STAT signaling pathway. Acta Histochem 116: 1331–1336.

Identyfikatory

DOI

10.21307/ane‑2018‑035