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Astrocytic activation in relation to inflammatory markers during clinical exacerbation of relapsing-remitting multiple sclerosis

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Summary

The study aimed to assay the cerebrospinal fluid (CSF) levels of protein S100B, a biomarker of astrocyte activation in relation to kynurenic acid (KYNA) and nitric oxide (NO) metabolites, nitrate/nitrite (NOx) concentrations in acute relapse multiple sclerosis (MS) patients. Twenty relapsing-remitting MS (RR-MS) patients and 10 controls were enrolled. RR-MS patients were assessed on the expanded disability status scale (EDSS) and underwent lumbar puncture. The CSF KYNA, NOx and S100B levels were significantly higher in RR-MS group compared to controls (p = 0.01, 0.001, 0.04, respectively). There was a significant correlation between CSF S100B and KYNA (p = 0.01) but not NOx (p > 0.05) in RR-MS. CSF KYNA, NOx or S100B concentrations did not correlate with disease characteristics of MS patients.

Our study suggests the activation of the kynurenine pathway leading to the increase of neuroprotective KYNA in the CSF of MS patients during acute relapse what contrasts with chronic phases of the disease.

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References

  • G Acar F Idiman E Idiman G Kirkali H Cakmakci S Ozakbas (2003) ArticleTitleNitric oxide as an activity marker in multiple sclerosis J Neurol 250 588–592 10.1007/s00415-003-1041-0 Occurrence Handle10.1007/s00415-003-1041-0 Occurrence Handle1:CAS:528:DC%2BD3sXlt12is78%3D Occurrence Handle12736739

    Article  CAS  PubMed  Google Scholar 

  • C Adami G Sorci E Blasi AL Agneletti F Bistoni R Donato (2001) ArticleTitleS100B expression in and effects on microglia Glia 33 131–142 10.1002/1098-1136(200102)33:2<131::AID-GLIA1012>3.0.CO;2-D Occurrence Handle10.1002/1098-1136(200102)33:2<131::AID-GLIA1012>3.0.CO;2-D Occurrence Handle1:STN:280:DC%2BD3M3isFShsw%3D%3D Occurrence Handle11180510

    Article  CAS  PubMed  Google Scholar 

  • L Bo TM Dawson S Wesselingh S Mork S Choi PA Kong D Hanley BD Trapp (1994) ArticleTitleInduction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains Ann Neurol 36 778–786 10.1002/ana.410360515 Occurrence Handle10.1002/ana.410360515 Occurrence Handle1:STN:280:DyaK2M%2FmvF2ntQ%3D%3D Occurrence Handle7526776

    Article  CAS  PubMed  Google Scholar 

  • A Chiarugi A Cozzi C Ballerini L Massacesi F Moroni (2001) ArticleTitleKynurenine 3-mono-oxygenase activity and neurotoxic kynurenine metabolites increase in the spinal cord of rats with experimental allergic encephalomyelitis Neuroscience 102 687–695 10.1016/S0306-4522(00)00504-2 Occurrence Handle10.1016/S0306-4522(00)00504-2 Occurrence Handle1:CAS:528:DC%2BD3MXhsVKlsrs%3D Occurrence Handle11226705

    Article  CAS  PubMed  Google Scholar 

  • R Donato (2003) ArticleTitleIntracellular and extracellular roles of S100 proteins Microsc Res Tech 60 540–551 10.1002/jemt.10296 Occurrence Handle10.1002/jemt.10296 Occurrence Handle1:CAS:528:DC%2BD3sXjt1ajsL8%3D Occurrence Handle12645002

    Article  CAS  PubMed  Google Scholar 

  • J Drulovic I Dujmovic S Mesaros T Samardzic D Maksimovic N Stojsavljevic Z Levic M Mostarica Stojokvic (2001) ArticleTitleRaised cerebrospinal fluid nitrite and nitrate levels in patients with multiple sclerosis: no correlation with disease activity Mult Scler 7 19–22 Occurrence Handle10.1191/135245801671221561 Occurrence Handle1:CAS:528:DC%2BD3MXjs1eisrc%3D Occurrence Handle11321188

    Article  CAS  PubMed  Google Scholar 

  • EM Frohman MK Racke CS Raine (2006) ArticleTitleMultiple sclerosis — the plaque and its pathogenesis N Engl J Med 354 942–955 10.1056/NEJMra052130 Occurrence Handle10.1056/NEJMra052130 Occurrence Handle1:CAS:528:DC%2BD28XitVertLc%3D Occurrence Handle16510748

    Article  CAS  PubMed  Google Scholar 

  • G Giovannoni (1998) ArticleTitleCerebrospinal fluid and serum nitric oxide metabolites in patients with multiple sclerosis Mult Scler 4 27–30 Occurrence Handle10.1191/135245898678909178 Occurrence Handle1:CAS:528:DyaK1cXitVGru78%3D Occurrence Handle9532589

    Article  CAS  PubMed  Google Scholar 

  • AJ Green G Keir EJ Thompson (1997) ArticleTitleA specific and sensitive ELISA for measuring S-100b in cerebrospinal fluid J Immunol Methods 205 35–41 10.1016/S0022-1759(97)00050-1 Occurrence Handle10.1016/S0022-1759(97)00050-1 Occurrence Handle1:CAS:528:DyaK2sXkslersb4%3D Occurrence Handle9236913

    Article  CAS  PubMed  Google Scholar 

  • GJ Guillemin DG Smith SJ Kerr GA Smythe V Kapoor PJ Armati BJ Brew (2000) ArticleTitleCharacterisation of kynurenine pathway metabolism in human astrocytes and implications in neuropathogenesis Redox Rep 5 108–111 10.1179/135100000101535375 Occurrence Handle10.1179/135100000101535375 Occurrence Handle1:CAS:528:DC%2BD3cXlvVemu7o%3D Occurrence Handle10939285

    Article  CAS  PubMed  Google Scholar 

  • Z Hartai P Klivenyi T Janaky B Penke L Dux L Vecsei (2005) ArticleTitleKynurenine metabolism in multiple sclerosis Acta Neurol Scand 112 93–96 10.1111/j.1600-0404.2005.00442.x Occurrence Handle10.1111/j.1600-0404.2005.00442.x Occurrence Handle1:CAS:528:DC%2BD2MXos1Crtbg%3D Occurrence Handle16008534

    Article  CAS  PubMed  Google Scholar 

  • MP Heyes CY Chen EO Major K Saito (1997) ArticleTitleDifferent kynurenine pathway enzymes limit quinolinic acid formation by various human cell types Biochem J 326 351–356 Occurrence Handle1:CAS:528:DyaK2sXmt1Gis70%3D Occurrence Handle9291104

    CAS  PubMed  Google Scholar 

  • KE Hill LV Zollinger HE Watt NG Carlson JW Rose (2004) ArticleTitleInducible nitric oxide synthase in chronic active multiple sclerosis plaques: distribution, cellular expression and association with myelin damage J Neuroimmunol 151 171–179 10.1016/j.jneuroim.2004.02.005 Occurrence Handle10.1016/j.jneuroim.2004.02.005 Occurrence Handle1:CAS:528:DC%2BD2cXktVOmtLc%3D Occurrence Handle15145615

    Article  CAS  PubMed  Google Scholar 

  • J Hu F Castets JL Guevara LJ Van Eldik (1996) ArticleTitleS100 beta stimulates inducible nitric oxide synthase activity and mRNA levels in rat cortical astrocytes J Biol Chem 271 2543–2547 10.1074/jbc.271.5.2543 Occurrence Handle10.1074/jbc.271.5.2543 Occurrence Handle1:CAS:528:DyaK28XptVKksg%3D%3D Occurrence Handle8576219

    Article  CAS  PubMed  Google Scholar 

  • AW Johnson JM Land EJ Thompson JP Bolanos JB Clark SJ Heales (1995) ArticleTitleEvidence for increased nitric oxide production in multiple sclerosis J Neurol Neurosurg Psychiatry 58 107 Occurrence Handle10.1136/jnnp.58.1.107 Occurrence Handle1:STN:280:DyaK2M7itlemtA%3D%3D Occurrence Handle7823050

    Article  CAS  PubMed  Google Scholar 

  • JF Kurtzke (1998) ArticleTitleRating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS) Neurology 33 1444–1452

    Google Scholar 

  • H Link (1998) ArticleTitleThe cytokine storm in multiple sclerosis Mult Scler 4 12–15 10.1191/135245898678909141 Occurrence Handle10.1191/135245898678909141 Occurrence Handle1:CAS:528:DyaK1cXitVGrurs%3D Occurrence Handle9532586

    Article  CAS  PubMed  Google Scholar 

  • JS Liu ML Zhao CF Brosnan SC Lee (2001) ArticleTitleExpression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions Am J Pathol 158 2057–2066 Occurrence Handle1:CAS:528:DC%2BD3MXkvFyksb0%3D Occurrence Handle11395383

    CAS  PubMed  Google Scholar 

  • C Malmestrom S Haghighi L Rosengren O Andersen J Lycke (2003) ArticleTitleNeurofilament light protein and glial fibrillary acidic protein as biological markers in MS Neurology 61 1720–1725 Occurrence Handle1:STN:280:DC%2BD3snhtV2ktQ%3D%3D Occurrence Handle14694036

    CAS  PubMed  Google Scholar 

  • AR Massaro F Michetti A Laudisio P Bergonzi (1985) ArticleTitleMyelin basic protein and S-100 antigen in cerebrospinal fluid of patients with multiple sclerosis in the acute phase Ital J Neurol Sci 6 53–56 10.1007/BF02229218 Occurrence Handle10.1007/BF02229218 Occurrence Handle1:STN:280:DyaL2M3gs1ygsw%3D%3D Occurrence Handle2581917

    Article  CAS  PubMed  Google Scholar 

  • KM Miranda MG Espey DA Wink (2001) ArticleTitleA rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite Nitric Oxide 5 62–71 10.1006/niox.2000.0319 Occurrence Handle10.1006/niox.2000.0319 Occurrence Handle1:CAS:528:DC%2BD3MXhtFemsrs%3D Occurrence Handle11178938

    Article  CAS  PubMed  Google Scholar 

  • H Nemeth J Toldi L Vecsei (2005) ArticleTitleRole of kynurenines in the central and peripheral nervous systems Curr Neurovasc Res 2 249–260 10.2174/1567202054368326 Occurrence Handle10.2174/1567202054368326 Occurrence Handle16181118

    Article  PubMed  Google Scholar 

  • EL Oleszak E Zaczynska M Bhattacharjee C Butunoi A Legido CD Katsetos (1998) ArticleTitleInducible nitric oxide synthase and nitrotyrosine are found in monocytes/macrophages and/or astrocytes in acute, but not in chronic, multiple sclerosis Clin Diagn Lab Immunol 5 438–445 Occurrence Handle1:CAS:528:DyaK1cXltVOrt7o%3D Occurrence Handle9665945

    CAS  PubMed  Google Scholar 

  • A Petzold MJ Eikelenboom D Gveric G Keir M Chapman RH Lazeron ML Cuzner CH Polman BM Uitdehaag EJ Thompson G Giovannoni (2002) ArticleTitleMarkers for different glial cell responses in multiple sclerosis: clinical and pathological correlations Brain 125 1462–1473 10.1093/brain/awf165 Occurrence Handle10.1093/brain/awf165 Occurrence Handle1:STN:280:DC%2BD38zjtlKktg%3D%3D Occurrence Handle12076997

    Article  CAS  PubMed  Google Scholar 

  • K Rejdak H Bartosik-Psujek B Dobosz T Kocki P Grieb G Giovannoni WA Turski Z Stelmasiak (2002) ArticleTitleDecreased level of kynurenic acid in cerebrospinal fluid of relapsing-onset multiple sclerosis patients Neurosci Lett 331 63–65 10.1016/S0304-3940(02)00710-3 Occurrence Handle10.1016/S0304-3940(02)00710-3 Occurrence Handle1:CAS:528:DC%2BD38XnsVajuro%3D Occurrence Handle12359324

    Article  CAS  PubMed  Google Scholar 

  • K Rejdak A Petzold MA Sharpe M Smith G Keir Z Stelmasiak EJ Thompson G Giovannoni (2003) ArticleTitleSerum and urine nitrate and nitrite are not reliable indicators of intrathecal nitric oxide production in acute brain injury J Neurol Sci 208 1–7 10.1016/S0022-510X(02)00412-4 Occurrence Handle10.1016/S0022-510X(02)00412-4 Occurrence Handle1:CAS:528:DC%2BD3sXhvFKjtL8%3D Occurrence Handle12639718

    Article  CAS  PubMed  Google Scholar 

  • K Rejdak MJ Eikelenboom A Petzold EJ Thompson Z Stelmasiak RH Lazeron F Barkhof CH Polman BM Uitdehaag G Giovannoni (2004) ArticleTitleCSF nitric oxide metabolites are associated with activity and progression of multiple sclerosis Neurology 63 1439–1445 Occurrence Handle1:CAS:528:DC%2BD2cXotFGrsrw%3D Occurrence Handle15505162

    CAS  PubMed  Google Scholar 

  • M Rovaris C Confavreux R Furlan L Kappos G Comi M Filippi (2006) ArticleTitleSecondary progressive multiple sclerosis: current knowledge and future challenges Lancet Neurol 5 343–354 10.1016/S1474-4422(06)70410-0 Occurrence Handle10.1016/S1474-4422(06)70410-0 Occurrence Handle16545751

    Article  PubMed  Google Scholar 

  • R Schwarcz R Pellicciari (2002) ArticleTitleManipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities J Pharmacol Exp Ther 303 1–10 10.1124/jpet.102.034439 Occurrence Handle10.1124/jpet.102.034439 Occurrence Handle1:CAS:528:DC%2BD38XnsV2ru7k%3D Occurrence Handle12235226

    Article  CAS  PubMed  Google Scholar 

  • KJ Smith H Lassmann (2002) ArticleTitleThe role of nitric oxide in multiple sclerosis Lancet Neurol 1 232–241 10.1016/S1474-4422(02)00102-3 Occurrence Handle10.1016/S1474-4422(02)00102-3 Occurrence Handle1:CAS:528:DC%2BD3sXkvFOgsLc%3D Occurrence Handle12849456

    Article  CAS  PubMed  Google Scholar 

  • A Svenningsson AS Petersson O Andersen GK Hansson (1999) ArticleTitleNitric oxide metabolites in CSF of patients with MS are related to clinical disease course Neurology 53 1880–1882 Occurrence Handle1:CAS:528:DyaK1MXnvVKns7g%3D Occurrence Handle10563648

    CAS  PubMed  Google Scholar 

  • WA Turski M Nakamura WP Todd BK Carpenter WO Whetsell SuffixJr R Schwarcz (1988) ArticleTitleIdentification and quantification of kynurenic acid in human brain tissue Brain Res 454 164–169 10.1016/0006-8993(88)90815-3 Occurrence Handle10.1016/0006-8993(88)90815-3 Occurrence Handle1:CAS:528:DyaL1cXks12ktrk%3D Occurrence Handle3409000

    Article  CAS  PubMed  Google Scholar 

  • HQ Wu A Rassoulpour JH Goodman HE Scharfman EH Bertram R Schwarcz (2005) ArticleTitleKynurenate and 7-chlorokynurenate formation in chronically epileptic rats Epilepsia 46 1010–1016 10.1111/j.1528-1167.2005.67404.x Occurrence Handle10.1111/j.1528-1167.2005.67404.x Occurrence Handle1:CAS:528:DC%2BD2MXosVCjtro%3D Occurrence Handle16026552

    Article  CAS  PubMed  Google Scholar 

  • T Yamashita Y Ando K Obayashi M Uchino M Ando (1997) ArticleTitleChanges in nitrite and nitrate (NO2-/NO3-) levels in cerebrospinal fluid of patients with multiple sclerosis J Neurol Sci 153 32–34 10.1016/S0022-510X(97)00183-4 Occurrence Handle10.1016/S0022-510X(97)00183-4 Occurrence Handle1:STN:280:DyaK1c7hsFGisg%3D%3D Occurrence Handle9455975

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Medical University of Lublin, Lublin, Poland

    K. Rejdak, J. Kurzepa & Z. Stelmasiak

  2. Department of Neuroinflammation, Institute of Neurology, UCL, London, U.K.

    A. Petzold

  3. Department of Pharmacology, Medical University of Lublin, Lublin, Poland

    T. Kocki & W. A. Turski

  4. Medical Research Center, Polish Academy of Sciences, Warsaw, Poland

    K. Rejdak & P. Grieb

  5. Department of Toxicology, Institute of Agricultural Medicine, Lublin, Poland

    W. A. Turski

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  1. K. Rejdak
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  2. A. Petzold
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  3. T. Kocki
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  4. J. Kurzepa
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  6. W. A. Turski
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  7. Z. Stelmasiak
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Rejdak, K., Petzold, A., Kocki, T. et al. Astrocytic activation in relation to inflammatory markers during clinical exacerbation of relapsing-remitting multiple sclerosis. J Neural Transm 114, 1011–1015 (2007). https://doi.org/10.1007/s00702-007-0667-y

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  • DOI: https://doi.org/10.1007/s00702-007-0667-y

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