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Targeting Enolase in Reducing Secondary Damage in Acute Spinal Cord Injury in Rats

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Abstract

Spinal cord injury (SCI) is a complex debilitating condition leading to permanent life-long neurological deficits. The complexity of SCI suggests that a concerted multi-targeted therapeutic approach is warranted to optimally improve function. Damage to spinal cord is complicated by an increased detrimental response from secondary injury factors mediated by activated glial cells and infiltrating macrophages. While elevation of enolase especially neuron specific enolase (NSE) in glial and neuronal cells is believed to trigger inflammatory cascades in acute SCI, alteration of NSE and its subsequent effects in acute SCI remains unknown. This study measured NSE expression levels and key inflammatory mediators after acute SCI and investigated the role of ENOblock, a novel small molecule inhibitor of enolase, in a male Sprague–Dawley (SD) rat SCI model. Serum NSE levels as well as cytokines/chemokines and metabolic factors were evaluated in injured animals following treatment with vehicle alone or ENOblock using Discovery assay. Spinal cord samples were also analyzed for NSE and MMPs 2 and 9 as well as glial markers by Western blotting. The results indicated a significant decrease in serum inflammatory cytokines/chemokines and NSE, alterations of metabolic factors and expression of MMPs in spinal cord tissues after treatment with ENOblock (100 µg/kg, twice). These results support the hypothesis that activation of glial cells and inflammation status can be modulated by regulation of NSE expression and activity. Analysis of SCI tissue samples by immunohistochemistry confirmed that ENOblock decreased gliosis which may have occurred through reduction of elevated NSE in rats. Overall, elevation of NSE is deleterious as it promotes extracellular degradation and production of inflammatory cytokines/chemokines and metabolic factors which activates glia and damages neurons. Thus, reduction of NSE by ENOblock may have potential therapeutic implications in acute SCI.

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References

  1. Pancholi V (2001) Multifunctional alpha-enolase: its role in diseases. Cell Mol Life Sci 58(7):902–920

    Article  CAS  PubMed  Google Scholar 

  2. Diaz-Ramos A, Roig-Borrellas A, Garcia-Melero A, Lopez-Alemany R (2012) Alpha-enolase, a multifunctional protein: its role on pathophysiological situations. J Biomed Biotechnol 2012:156795. doi:10.1155/2012/156795

    Article  PubMed  PubMed Central  Google Scholar 

  3. Chen SH, Giblett ER (1976) Enolase: human tissue distribution and evidence for three different loci. Ann Hum Genet 39(3):277–280

    Article  CAS  PubMed  Google Scholar 

  4. Fan SS, Zong M, Zhang H, Lu Y, Lu TB, Fan LY (2015) Decreased expression of alpha-enolase inhibits the proliferation of hypoxia-induced rheumatoid arthritis fibroblasts-like synoviocytes. Modern Rheumatol 25(5):701–707. doi:10.3109/14397595.2015.1014141.

    Article  Google Scholar 

  5. Kuehn A, Fischer J, Hilger C, Sparla C, Biedermann T, Hentges F (2014) Correlation of clinical monosensitivity to cod with specific IgE to enolase and aldolase. Ann Allergy Asthma Immunol 670-1(6):e2. doi:10.1016/j.anai.2014.09.005

    Google Scholar 

  6. Fukano K, Kimura K (2014) Measurement of enolase activity in cell lysates. Methods Enzymol 542:115–124. doi:10.1016/B978-0-12-416618-9.00006-6

    Article  CAS  PubMed  Google Scholar 

  7. Vermeulen N, Arijs I, Joossens S, Vermeire S, Clerens S, Van den Bergh K et al (2008) Anti-alpha-enolase antibodies in patients with inflammatory Bowel disease. Clin Chem 54(3):534–541. doi:10.1373/clinchem.2007.098368

    Article  CAS  PubMed  Google Scholar 

  8. Bock A, Tucker N, Kelher MR, Khan SY, Gonzalez E, Wohlauer M et al (2015) Alpha-enolase causes proinflammatory activation of pulmonary microvascular endothelial cells and primes neutrophils through plasmin activation of protease-activated receptor 2. Shock 44(2):137–142. doi:10.1097/SHK.0000000000000394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Haque A, Ray SK, Cox A, Banik NL (2016) Neuron specific enolase: a promising therapeutic target in acute spinal cord injury. Metab Brain Dis 31(3):487–495. doi:10.1007/s11011-016-9801-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Woodcock T, Morganti-Kossmann MC (2013) The role of markers of inflammation in traumatic brain injury. Front Neurol 4:18. doi:10.3389/fneur.2013.00018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hajdukova L, Sobek O, Prchalova D, Bilkova Z, Koudelkova M, Lukaskova J et al (2015) Biomarkers of brain damage: S100B and NSE concentrations in cerebrospinal fluid: a normative study. BioMed Res Int 2015:379071. doi:10.1155/2015/379071

    Article  PubMed  PubMed Central  Google Scholar 

  12. Pouw MH, Hosman AJ, van Middendorp JJ, Verbeek MM, Vos PE, van de Meent H (2009) Biomarkers in spinal cord injury. Spinal Cord 47(7):519–525. doi:10.1038/sc.2008.176

    Article  CAS  PubMed  Google Scholar 

  13. Cheng F, Yuan Q, Yang J, Wang W, Liu H (2014) The prognostic value of serum neuron-specific enolase in traumatic brain injury: systematic review and meta-analysis. PLoS ONE 9(9):e106680. doi:10.1371/journal.pone.0106680

    Article  PubMed  PubMed Central  Google Scholar 

  14. Johnsson P, Blomquist S, Luhrs C, Malmkvist G, Alling C, Solem JO et al (2000) Neuron-specific enolase increases in plasma during and immediately after extracorporeal circulation. Ann Thorac Surg 69(3):750–754

    Article  CAS  PubMed  Google Scholar 

  15. Ergun R, Bostanci U, Akdemir G, Beskonakli E, Kaptanoglu E, Gursoy F et al (1998) Prognostic value of serum neuron-specific enolase levels after head injury. Neurol Res 20(5):418–420

    Article  CAS  PubMed  Google Scholar 

  16. Shih NY, Lai HL, Chang GC, Lin HC, Wu YC, Liu JM et al (2010) Anti-alpha-enolase autoantibodies are down-regulated in advanced cancer patients. Jpn J Clin Oncol 40(7):663–669. doi:10.1093/jjco/hyq028

    Article  PubMed  Google Scholar 

  17. Wygrecka M, Marsh LM, Morty RE, Henneke I, Guenther A, Lohmeyer J et al (2009) Enolase-1 promotes plasminogen-mediated recruitment of monocytes to the acutely inflamed lung. Blood 113(22):5588–5598. doi:10.1182/blood-2008-08-170837

    Article  CAS  PubMed  Google Scholar 

  18. Kwon BK, Tetzlaff W, Grauer JN, Beiner J, Vaccaro AR (2004) Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J 4(4):451–464. doi:10.1016/j.spinee.2003.07.007

    Article  PubMed  Google Scholar 

  19. McDonald JW, Sadowsky C (2002) Spinal-cord injury. Lancet 359(9304):417–425. doi:10.1016/S0140-6736(02)07603-1

    Article  PubMed  Google Scholar 

  20. Banik NL, Matzelle DC, Gantt-Wilford G, Osborne A, Hogan EL (1997) Increased calpain content and progressive degradation of neurofilament protein in spinal cord injury. Brain Res 752(1–2):301–306

    Article  CAS  PubMed  Google Scholar 

  21. Yu CG, Joshi A, Geddes JW (2008) Intraspinal MDL28170 microinjection improves functional and pathological outcome following spinal cord injury. J Neurotrauma 25(7):833–840. doi:10.1089/neu.2007.0490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Banik NL, Hogan EL, Hsu CY (1987) The multimolecular cascade of spinal cord injury. Studies on prostanoids, calcium, and proteinases. Neurochem Pathol 7(1):57–77

    Article  CAS  PubMed  Google Scholar 

  23. Sousa LP, Silva BM, Brasil BS, Nogueira SV, Ferreira PC, Kroon EG et al (2005) Plasminogen/plasmin regulates alpha-enolase expression through the MEK/ERK pathway. Biochem Biophys Res Commun 337(4):1065–1071. doi:10.1016/j.bbrc.2005.09.154

    Article  CAS  PubMed  Google Scholar 

  24. Cao F, Yang XF, Liu WG, Hu WW, Li G, Zheng XJ et al (2008) Elevation of neuron-specific enolase and S-100beta protein level in experimental acute spinal cord injury. J Clin Neurosci 15(5):541–544. doi:10.1016/j.jocn.2007.05.014

    Article  CAS  PubMed  Google Scholar 

  25. Sawhney S, Hood K, Shaw A, Braithwaite AW, Stubbs R, Hung NA et al (2015) Alpha-enolase is upregulated on the cell surface and responds to plasminogen activation in mice expressing a 133p53alpha mimic. PLoS ONE 10(2):e0116270. doi:10.1371/journal.pone.0116270

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hafner A, Obermajer N, Kos J (2012) Gamma-enolase C-terminal peptide promotes cell survival and neurite outgrowth by activation of the PI3K/Akt and MAPK/ERK signalling pathways. Biochem J 443(2):439–450. doi:10.1042/BJ20111351

    Article  CAS  PubMed  Google Scholar 

  27. Bae S, Kim H, Lee N, Won C, Kim HR, Hwang YI et al (2012) Alpha-enolase expressed on the surfaces of monocytes and macrophages induces robust synovial inflammation in rheumatoid arthritis. J Immunol 189(1):365–372. doi:10.4049/jimmunol.1102073

    Article  CAS  PubMed  Google Scholar 

  28. Hawryluk GW, Rowland J, Kwon BK, Fehlings MG (2008) Protection and repair of the injured spinal cord: a review of completed, ongoing, and planned clinical trials for acute spinal cord injury. Neurosurg Focus 25(5):E14. doi:10.3171/foc.2008.25.11.e14

    Article  PubMed  Google Scholar 

  29. Bragge P, Piccenna L, Middleton J, Williams S, Creasey G, Dunlop S et al (2015) Developing a spinal cord injury research strategy using a structured process of evidence review and stakeholder dialogue. Part II: background to a research strategy. Spinal cord 53(10):721–728. doi:10.1038/sc.2015.86

    Article  CAS  PubMed  Google Scholar 

  30. Chamberlain JD, Meier S, Mader L, von Groote PM, Brinkhof MW (2015) Mortality and longevity after a spinal cord injury: systematic review and meta-analysis. Neuroepidemiology 44(3):182–198. doi:10.1159/000382079

    Article  PubMed  Google Scholar 

  31. Varma AK, Das A, Wallace Gt, Barry J, Vertegel AA, Ray SK et al (2013) Spinal cord injury: a review of current therapy, future treatments, and basic science frontiers. Neurochem Res 38(5):895–905. doi:10.1007/s11064-013-0991-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Tator CH, Hashimoto R, Raich A, Norvell D, Fehlings MG, Harrop JS et al (2012) Translational potential of preclinical trials of neuroprotection through pharmacotherapy for spinal cord injury. J Neurosurg Spine 17(1 Suppl):157–229. doi:10.3171/2012.5.AOSPINE12116

    Article  PubMed  Google Scholar 

  33. Lim JH, Muguet-Chanoit AC, Smith DT, Laber E, Olby NJ (2014) Potassium channel antagonists 4-aminopyridine and the T-butyl carbamate derivative of 4-aminopyridine improve hind limb function in chronically non-ambulatory dogs; a blinded, placebo-controlled trial. PLoS ONE 9(12):e116139. doi:10.1371/journal.pone.0116139

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wang TG, Xu J, Zhu AH, Lu H, Miao ZN, Zhao P et al (2016) Human amniotic epithelial cells combined with silk fibroin scaffold in the repair of spinal cord injury. Neural Regen Res 11(10):1670–1677. doi:10.4103/1673-5374.193249

    Article  PubMed  PubMed Central  Google Scholar 

  35. Crupi R, Impellizzeri D, Bruschetta G, Cordaro M, Paterniti I, Siracusa R et al (2016) Co-ultramicronized palmitoylethanolamide/luteolin promotes neuronal regeneration after spinal cord injury. Front Pharmacol 7:47. doi:10.3389/fphar.2016.00047

    Article  PubMed  PubMed Central  Google Scholar 

  36. Deng L, Ruan Y, Chen C, Frye CC, Xiong W, Jin X et al (2016) Characterization of dendritic morphology and neurotransmitter phenotype of thoracic descending propriospinal neurons after complete spinal cord transection and GDNF treatment. Exp Neurol 277:103–114. doi:10.1016/j.expneurol.2015.12.018

    Article  CAS  PubMed  Google Scholar 

  37. Li X, Han J, Zhao Y, Ding W, Wei J, Li J et al (2016) Functionalized collagen scaffold implantation and cAMP administration collectively facilitate spinal cord regeneration. Acta Biomater 30:233–245. doi:10.1016/j.actbio.2015.11.023

    Article  PubMed  Google Scholar 

  38. Gabel BC, Curtis EI, Marsala M, Ciacci JD (2016) A review of stem cell therapy for spinal cord injury: large animal models and the frontier in humans. World Neurosurg. doi:10.1016/j.wneu.2016.11.053

    Google Scholar 

  39. Wang Z, Winsor K, Neinhaus C, Hess E, Blackmore MG (2016) Combined chondroitinase and KLF7 expression reduce net retraction of sensory and CST axons from sites of spinal injury. Neurobiol Dis. doi:10.1016/j.nbd.2016.12.010

    Google Scholar 

  40. Chakrabarti M, Das A, Samantaray S, Smith JA, Banik NL, Haque A et al (2015) Molecular mechanisms of estrogen for neuroprotection in spinal cord injury and traumatic brain injury. Rev Neurosci. doi:10.1515/revneuro-2015-0032

    Google Scholar 

  41. Chakrabarti M, Haque A, Banik NL, Nagarkatti P, Nagarkatti M, Ray SK (2014) Estrogen receptor agonists for attenuation of neuroinflammation and neurodegeneration. Brain Res Bull 109:22–31. doi:10.1016/j.brainresbull.2014.09.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Samantaray S, Das A, Matzelle DC, Yu SP, Wei L, Varma A et al (2016) Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats. J Neurochem 137(4):604–617. doi:10.1111/jnc.13610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Samantaray S, Das A, Matzelle DC, Yu SP, Wei L, Varma A et al (2016) Administration of low dose estrogen attenuates gliosis and protects neurons in acute spinal cord injury in rats. J Neurochem 136(5):1064–1073. doi:10.1111/jnc.13464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cox A, Varma A, Barry J, Vertegel A, Banik N (2015) Nanoparticle estrogen in rat spinal cord injury elicits rapid anti-inflammatory effects in plasma, cerebrospinal fluid, and tissue. J Neurotrauma 32(18):1413–1421. doi:10.1089/neu.2014.3730

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ondruschka B, Pohlers D, Sommer G, Schober K, Teupser D, Franke H et al (2013) S100B and NSE as useful postmortem biochemical markers of traumatic brain injury in autopsy cases. J Neurotrauma 30(22):1862–1871. doi:10.1089/neu.2013.2895

    Article  PubMed  Google Scholar 

  46. Li M, Wen H, Yan Z, Ding T, Long L, Qin H et al (2014) Temporal-spatial expression of ENOLASE after acute spinal cord injury in adult rats. Neurosci Res 79:76–82. doi:10.1016/j.neures.2013.12.001

    Article  CAS  PubMed  Google Scholar 

  47. Jung DW, Kim WH, Park SH, Lee J, Kim J, Su D et al (2013) A unique small molecule inhibitor of enolase clarifies its role in fundamental biological processes. ACS Chem Biol 8(6):1271–1282. doi:10.1021/cb300687k

    Article  CAS  PubMed  Google Scholar 

  48. Perot PL Jr., Lee WA, Hsu CY, Hogan EL, Cox RD, Gross AJ (1987) Therapeutic model for experimental spinal cord injury in the rat: I. Mortality and motor deficit. Cent Nerv Syst Trauma 4(3):149–159

    Article  PubMed  Google Scholar 

  49. Ray SK, Matzelle DD, Wilford GG, Hogan EL, Banik NL (2001) Inhibition of calpain-mediated apoptosis by E-64 d-reduced immediate early gene (IEG) expression and reactive astrogliosis in the lesion and penumbra following spinal cord injury in rats. Brain Res 916(1–2):115–126

    Article  CAS  PubMed  Google Scholar 

  50. Kupina NC, Nath R, Bernath EE, Inoue J, Mitsuyoshi A, Yuen PW et al (2001) The novel calpain inhibitor SJA6017 improves functional outcome after delayed administration in a mouse model of diffuse brain injury. J Neurotrauma 18(11):1229–1240. doi:10.1089/089771501317095269

    Article  CAS  PubMed  Google Scholar 

  51. Das A, Sribnick EA, Wingrave JM, Del Re AM, Woodward JJ, Appel SH et al (2005) Calpain activation in apoptosis of ventral spinal cord 4.1 (VSC4.1) motoneurons exposed to glutamate: calpain inhibition provides functional neuroprotection. J Neurosci Res 81(4):551–562. doi:10.1002/jnr.20581

    Article  CAS  PubMed  Google Scholar 

  52. Sharma AK, Rohrer B (2007) Sustained elevation of intracellular cGMP causes oxidative stress triggering calpain-mediated apoptosis in photoreceptor degeneration. Curr Eye Res 32(3):259–269. doi:10.1080/02713680601161238

    Article  CAS  PubMed  Google Scholar 

  53. Zhao D, Amria S, Hossain A, Sundaram K, Komlosi P, Nagarkatti M et al (2011) Enhancement of HLA class II-restricted CD4 + T cell recognition of human melanoma cells following treatment with bryostatin-1. Cell Immunol 271(2):392–400. doi:10.1016/j.cellimm.2011.08.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Haque MA, Li P, Jackson SK, Zarour HM, Hawes JW, Phan UT et al (2002) Absence of gamma-interferon-inducible lysosomal thiol reductase in melanomas disrupts T cell recognition of select immunodominant epitopes. J Exp Med 195(10):1267–1277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ray SK, Shields DC, Saido TC, Matzelle DC, Wilford GG, Hogan EL et al (1999) Calpain activity and translational expression increased in spinal cord injury. Brain Res 816(2):375–380

    Article  CAS  PubMed  Google Scholar 

  56. Widenfalk J, Lipson A, Jubran M, Hofstetter C, Ebendal T, Cao Y et al (2003) Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury. Neuroscience 120(4):951–960

    Article  CAS  PubMed  Google Scholar 

  57. Radwan FF, Zhang L, Hossain A, Doonan BP, God JM, Haque A (2012) Mechanisms regulating enhanced human leukocyte antigen class II-mediated CD4 + T cell recognition of human B-cell lymphoma by resveratrol. Leuk Lymphoma 53(2):305–314. doi:10.3109/10428194.2011.615423

    Article  CAS  PubMed  Google Scholar 

  58. Goldstein OG, Hajiaghamohseni LM, Amria S, Sundaram K, Reddy SV, Haque A (2008) Gamma-IFN-inducible-lysosomal thiol reductase modulates acidic proteases and HLA class II antigen processing in melanoma. Cancer Immunol Immunother 57(10):1461–1470. doi:10.1007/s00262-008-0483-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Shields DC, Tyor WR, Deibler GE, Hogan EL, Banik NL (1998) Increased calpain expression in activated glial and inflammatory cells in experimental allergic encephalomyelitis. Proc Natl Acad Sci USA 95(10):5768–5772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Guyton MK, Brahmachari S, Das A, Samantaray S, Inoue J, Azuma M et al (2009) Inhibition of calpain attenuates encephalitogenicity of MBP-specific T cells. J Neurochem 110(6):1895–1907. doi:10.1111/j1471-4159.2009.06287.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Yune TY, Chang MJ, Kim SJ, Lee YB, Shin SW, Rhim H et al (2003) Increased production of tumor necrosis factor-alpha induces apoptosis after traumatic spinal cord injury in rats. J Neurotrauma 20(2):207–219. doi:10.1089/08977150360547116

    Article  PubMed  Google Scholar 

  62. Wang CX, Olschowka JA, Wrathall JR (1997) Increase of interleukin-1beta mRNA and protein in the spinal cord following experimental traumatic injury in the rat. Brain Res 759(2):190–196

    Article  CAS  PubMed  Google Scholar 

  63. Ousman SS, David S (2001) MIP-1alpha, MCP-1, GM-CSF, and TNF-alpha control the immune cell response that mediates rapid phagocytosis of myelin from the adult mouse spinal cord. J Neurosci 21(13):4649–4656

    CAS  PubMed  Google Scholar 

  64. Wang J, Vodovotz Y, Fan L, Li Y, Liu Z, Namas R et al (2015) Injury-induced MRP8/MRP14 stimulates IP-10/CXCL10 in monocytes/macrophages. FASEB J 29(1):250–262. doi:10.1096/fj.14-255992

    Article  CAS  PubMed  Google Scholar 

  65. Mohty AM, Grob JJ, Mohty M, Richard MA, Olive D, Gaugler B (2010) Induction of IP-10/CXCL10 secretion as an immunomodulatory effect of low-dose adjuvant interferon-alpha during treatment of melanoma. Immunobiology 215(2):113–123. doi:10.1016/j.imbio.2009.03.008

    Article  CAS  PubMed  Google Scholar 

  66. Buttmann M, Merzyn C, Rieckmann P (2004) Interferon-beta induces transient systemic IP-10/CXCL10 chemokine release in patients with multiple sclerosis. J Neuroimmunol 156(1–2):195–203. doi:10.1016/j.jneuroim.2004.07.016

    Article  CAS  PubMed  Google Scholar 

  67. Magee KE, Kelsey CE, Kurzinski KL, Ho J, Mlakar LR, Feghali-Bostwick CA et al (2013) Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma. Arthritis Res Ther 15(6):R188. doi:10.1186/ar4378

    Article  PubMed  PubMed Central  Google Scholar 

  68. Haidet J, Cifarelli V, Trucco M, Luppi P (2009) Anti-inflammatory properties of C-Peptide. The review of diabetic studies. RDS 6(3):168–179. doi:10.1900/RDS.2009.6.168

    PubMed  PubMed Central  Google Scholar 

  69. Iikuni N, Lam QL, Lu L, Matarese G, La Cava A (2008) Leptin and inflammation. Curr Immunol Rev 4(2):70–79. doi:10.2174/157339508784325046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hou X, Sun L, Li Z, Mou H, Yu Z, Li H et al (2011) Associations of amylin with inflammatory markers and metabolic syndrome in apparently healthy Chinese. PLoS ONE 6(9):e24815. doi:10.1371/journal.pone.0024815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Guillamet E, Creus A, Ponti J, Sabbioni E, Fortaner S, Marcos R (2004) In vitro DNA damage by arsenic compounds in a human lymphoblastoid cell line (TK6) assessed by the alkaline Comet assay. Mutagenesis 19(2):129–135

    Article  CAS  PubMed  Google Scholar 

  72. Martinez VD, Thu KL, Vucic EA, Hubaux R, Adonis M, Gil L et al (2013) Whole-genome sequencing analysis identifies a distinctive mutational spectrum in an arsenic-related lung tumor. J Thorac Oncol 8(11):1451–1455. doi:10.1097/JTO.0b013e3182a4dd8e

    Article  CAS  PubMed  Google Scholar 

  73. Pleines UE, Morganti-Kossmann MC, Rancan M, Joller H, Trentz O, Kossmann T (2001) S-100 beta reflects the extent of injury and outcome, whereas neuronal specific enolase is a better indicator of neuroinflammation in patients with severe traumatic brain injury. J Neurotrauma 18(5):491–498. doi:10.1089/089771501300227297

    Article  CAS  PubMed  Google Scholar 

  74. Kulbe JR, Geddes JW (2016) Current status of fluid biomarkers in mild traumatic brain injury. Exp Neurol 275(Pt 3):334–352. doi:10.1016/j.expneurol.2015.05.004

    Article  CAS  PubMed  Google Scholar 

  75. Anand N, Stead LG (2005) Neuron-specific enolase as a marker for acute ischemic stroke: a systematic review. Cerebrovasc Dis 20(4):213–219. doi:10.1159/000087701

    Article  CAS  PubMed  Google Scholar 

  76. Martens P, Raabe A, Johnsson P (1998) Serum S-100 and neuron-specific enolase for prediction of regaining consciousness after global cerebral ischemia. Stroke 29(11):2363–2366

    Article  CAS  PubMed  Google Scholar 

  77. Pfeifer R, Borner A, Krack A, Sigusch HH, Surber R, Figulla HR (2005) Outcome after cardiac arrest: predictive values and limitations of the neuroproteins neuron-specific enolase and protein S-100 and the Glasgow Coma Scale. Resuscitation 65(1):49–55. doi:10.1016/j.resuscitation.2004.10.011

    Article  CAS  PubMed  Google Scholar 

  78. Mahata J, Chaki M, Ghosh P, Das LK, Baidya K, Ray K et al (2004) Chromosomal aberrations in arsenic-exposed human populations: a review with special reference to a comprehensive study in West Bengal, India. Cytogenet Genome Res 104(1–4):359–364. doi:10.1159/000077516

    Article  CAS  PubMed  Google Scholar 

  79. Faita F, Cori L, Bianchi F, Andreassi MG (2013) Arsenic-induced genotoxicity and genetic susceptibility to arsenic-related pathologies. Int J Environ Res Public Health 10(4):1527–1546. doi:10.3390/ijerph10041527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Sciandrello G, Barbaro R, Caradonna F, Barbata G (2002) Early induction of genetic instability and apoptosis by arsenic in cultured Chinese hamster cells. Mutagenesis 17(2):99–103

    Article  CAS  PubMed  Google Scholar 

  81. Thelin EP, Jeppsson E, Frostell A, Svensson M, Mondello S, Bellander BM et al (2016) Utility of neuron-specific enolase in traumatic brain injury; relations to S100B levels, outcome, and extracranial injury severity. Critic Care 20:285. doi:10.1186/s13054-016-1450-y

    Article  Google Scholar 

  82. McKinley W, Cifu D, Seel R, Huang M, Kreutzer J, Drake D et al (2003) Age-related outcomes in persons with spinal cord injury: a summary paper. NeuroRehabilitation 18(1):83–90

    PubMed  Google Scholar 

  83. God JM, Zhao D, Cameron CA, Amria S, Bethard JR, Haque A (2014) Disruption of HLA class II antigen presentation in Burkitt lymphoma: implication of a 47,000 MW acid labile protein in CD4 + T cell recognition. Immunology 142(3):492–505. doi:10.1111/imm.12281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Haidet J, Cifarelli V, Trucco M, Luppi P (2012) C-peptide reduces pro-inflammatory cytokine secretion in LPS-stimulated U937 monocytes in condition of hyperglycemia. Inflamm Res 61(1):27–35. doi:10.1007/s00011-011-0384-8

    Article  CAS  PubMed  Google Scholar 

  85. Fernandez-Riejos P, Najib S, Santos-Alvarez J, Martin-Romero C, Perez-Perez A, Gonzalez-Yanes C et al (2010) Role of leptin in the activation of immune cells. Mediators Inflamm 2010:568343. doi:10.1155/2010/568343

    Article  PubMed  PubMed Central  Google Scholar 

  86. Gitter BD, Cox LM, Carlson CD, May PC (2000) Human amylin stimulates inflammatory cytokine secretion from human glioma cells. Neuroimmunomodulation 7(3):147–152

    Article  CAS  PubMed  Google Scholar 

  87. Floden AM, Watt JA, Brissette CA (2011) Borrelia burgdorferi enolase is a surface-exposed plasminogen binding protein. PLoS ONE 6(11):e27502. doi:10.1371/journal.pone.0027502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hardemark HG, Persson L, Bolander HG, Hillered L, Olsson Y, Pahlman S (1988) Neuron-specific enolase is a marker of cerebral ischemia and infarct size in rat cerebrospinal fluid. Stroke 19(9):1140–1144

    Article  CAS  PubMed  Google Scholar 

  89. Horn M, Seger F, Schlote W (1995) Neuron-specific enolase in gerbil brain and serum after transient cerebral ischemia. Stroke 26(2):290–296 (discussion 6–7)

    Article  CAS  PubMed  Google Scholar 

  90. Joseph B, Pandit V, Zangbar B, Kulvatunyou N, Khalil M, Tang A et al (2015) Secondary brain injury in trauma patients: the effects of remote ischemic conditioning. J Trauma Acute Care Surg 78(4):698–703. doi:10.1097/TA.0000000000000584 (discussion 5)

    Article  PubMed  Google Scholar 

  91. Yu CG, Geddes JW (2007) Sustained calpain inhibition improves locomotor function and tissue sparing following contusive spinal cord injury. Neurochem Res 32(12):2046–2053. doi:10.1007/s11064-007-9347-4

    Article  CAS  PubMed  Google Scholar 

  92. Dumont RJ, Okonkwo DO, Verma S, Hurlbert RJ, Boulos PT, Ellegala DB et al (2001) Acute spinal cord injury, part I: pathophysiologic mechanisms. Clin Neuropharmacol 24(5):254–264

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the South Carolina Spinal Cord Injury Research Fund (SCIRF 2015 P-01 and SCIRF #2016 I-03 to A. Haque), National Institutes of Health (R01 CA129560 to A. Haque), and the Veterans Administration (I01 BX001262 and I01 BX002349 to N. Banik). We thank Ms. Margaret Romano of Histology and Immunohistochemistry Laboratory at the Department of Pathology and Laboratory Medicine at MUSC for her technical assistance with the immunohistochemistry.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, BSB-201, Charleston, SC, 29425, USA

    Azizul Haque, Mollie Capone & Naren L. Banik

  2. Department of Neurosurgery, Medical University of South Carolina, Charleston, USA

    Denise Matzelle & Naren L. Banik

  3. Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA

    Mollie Capone, Denise Matzelle & Naren L. Banik

  4. FirstString Research, Mt. Pleasant, SC, USA

    April Cox

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  1. Azizul Haque
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  2. Mollie Capone
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  3. Denise Matzelle
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  4. April Cox
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  5. Naren L. Banik
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Correspondence to Azizul Haque.

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Haque, A., Capone, M., Matzelle, D. et al. Targeting Enolase in Reducing Secondary Damage in Acute Spinal Cord Injury in Rats. Neurochem Res 42, 2777–2787 (2017). https://doi.org/10.1007/s11064-017-2291-z

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  • DOI: https://doi.org/10.1007/s11064-017-2291-z

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