Skip to main content
SpringerLink
Log in

The Differences in the Cellular and Plasma Antioxidative Capacity Between Transient and Defined Focal Brain Ischemia: Does it Suggest Supporting Time-Dependent Neuroprotection Therapy?

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

There are many opened questions about the precocious role of oxidative stress in the physiopathology of the early stage of transitory ischemic attack (TIA) and defined focal brain ischemia, as well as about its correlation with clinical severity, short-lasting and clinical outcome prediction in these conditions. The study evaluates the values of glutathione (GSH), glutathione peroxidase, and superoxide dismutase (SOD) in hemolysates and total thiol content (–SH), advanced oxidation protein products (AOPP), SOD, and malondialdehyde (MDA) in plasma, in TIA and stroke patients in the early stage of their neurological onset. The results are interpreted in view of the potential relationship between tested parameters and clinical severity and clinical outcome prediction. Better hemolysates’ and total antioxidant profile with higher values of AOPP were observed in TIA compared to stroke patients (p < 0.05). The stroke patients with initially better clinical presentation showed better antioxidant profile with lower values of AOPP (p < 0.05). In TIA patients, this was observed for GSH, –SH content, and AOPP (p < 0.05), which correlated with a short risk for stroke occurrence in this group (p < 0.01). Beyond MDA values, all tested parameters showed correlation with clinical outcome in stroke patients (p < 0.05). The measurement of oxidative stress in TIA and stroke patients would be important for identifying patients’ subgroups which might receive supporting therapy providing better neurological recovery and clinical outcome. That approach might give us an additional view of a short-lasting risk of stroke occurrence after TIA, and its clinical outcome and prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Andreeva IL, Kozemjakin AL, Kiskun AA (1988) Modifikacija metoda opredelenia perekisej lipidov v teste s tiobarbiturovojm kislotoj. Lab Delo 11:41–43

    PubMed  Google Scholar 

  • Ayala C, Greenlund KJ, Croft JB, Keenan NL, Donehoo RS, Giles WH et al (2001) Racial/ethnic disparities in mortality by stroke subtype in the United States, 1995–1998. Am J Epidemiol 154:1057–1063

    Article  CAS  PubMed  Google Scholar 

  • Bonita R, Beaglehole R (1988) Recovery of motor function after stroke. Stroke 19:1497–1500

    Article  CAS  PubMed  Google Scholar 

  • Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsan WG, Biller J et al (1989) Measurements of acute cerebral infarction: a clinical examination scale. Stroke 20:864–870

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA, Kanski J (2001) Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech Ageing Dev 122:945–962

    Article  CAS  PubMed  Google Scholar 

  • Caplan LR (2004) Treatment of acute stroke: still struggling. JAMA 292:1883–1885

    Article  CAS  PubMed  Google Scholar 

  • Cherubini A, Ruggiero C, Polidori MC, Mecocci P (2005) Potential markers of oxidative stress in stroke. Free Radic Biol Med 39:841–852

    Article  CAS  PubMed  Google Scholar 

  • De Haan JB, Crack PJ, Flentjar N, Iannello RC, Hertzog PJ, Kola I (2003) An imbalance in antioxidant defense affects cellular function: the pathophysiological consequences of a reduction in antioxidant defense in the glutathione peroxidase-1 (Gpx1) knock-out mouse. Redox Rep 8(2):69–79

    Article  PubMed  Google Scholar 

  • Demirkaya S, Topcuoglu MA, Aydin A, Ulas UH, Isimer AI, Vural O (2001) Malondialdehyde, glutathione peroxidase and super-oxide dismutase in peripheral blood erythrocytes of patients with acute cerebral ischemia. Eur J Neurol 8:43–51

    Article  CAS  PubMed  Google Scholar 

  • Domínguez C, Delgado P, Vilches A, Martín-Gallan P, Ribo M, Santamarina E et al (2010) Oxidative stress after thrombolysis-induced reperfusion in human stroke. Stroke 41:653–660

    Article  PubMed  Google Scholar 

  • Drabkin DL (1946) The crystallographic and optical properties of the haemoglobin of man in com-parison with those of other species. J Biol Chem 164:703–723

    CAS  PubMed  Google Scholar 

  • Easton JD, Saver JL, Albers GW, Alberts MJ, Chaturvedi S, Feldmann E et al (2009) Definition and evaluation of transient ischemic attack. A scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. Stroke 40:2276–2293

    Article  PubMed  Google Scholar 

  • El Kossi MM, Zakhary MM (2000) Oxidative stress in the context of acute cerebrovascular stroke. Stroke 31:1889–1892

    Article  PubMed  Google Scholar 

  • Ellman G (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  PubMed  Google Scholar 

  • Gariballa SE, Hutchin TP, Sinclair AJ (2002) Antioxidant capacity after acute ischaemic stroke. QJM 95:685–690

    Article  CAS  PubMed  Google Scholar 

  • Gursoy-Ozdemir Y, Can A, Dalkara T (2004) Reperfusion-induced oxidative/nitrative injury to neurovascular unit after focal cerebral ischemia. Stroke 35:1449–1453

    Article  PubMed  Google Scholar 

  • Johnston SC, Rothwell PM, Nguyen-Huynh MN, Giles MF, Elkins JS, Bernstein AL et al (2007) Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet 369:283–292

    Article  PubMed  Google Scholar 

  • Kasner SE, Chalela JA, Luciano JM, Cucchiara BL, Raps EC, McGarvey ML et al (1999) Reliability and validity of estimating the NIH stroke scale score from medical records. Stroke 30:1534–1537

    Article  CAS  PubMed  Google Scholar 

  • Lapchak PA, Zivin JA (2003) Ebselen, a seleno-organic antioxidant, is neuroprotective after embolic strokes in rabbits. Synergism with low-dose tissue plasminogen activator. Stroke 34:2013–2018

    Article  CAS  PubMed  Google Scholar 

  • Ljubisavljevic S, Stojanovic I, Vojinovic S, Stojanov D, Stojanovic S, Cvetkovic T et al (2013) The patients with clinically isolated syndrome and relapsing remitting multiples sclerosis show different levels of advanced protein oxidation products and reduced thiols content in sera and CSF. Neurochem Int 62(7):988–997

    Article  CAS  PubMed  Google Scholar 

  • Mackensen GB, Pate M, Sheng H, Calvi CL, Batinic-Haberle I, Day BJ et al (2001) Neuroprotection from delayed postischemic administration of a metalloporphyrin catalytic antioxidant. J Neurosci 21(13):4582–4592

    CAS  PubMed  Google Scholar 

  • Manzanero S, Santro T, Arumugam TV (2013) Neuronal oxidative stress in acute ischemic stroke: sources and contribution to cell injury. Neurochem Int 62:712–718

    Article  CAS  PubMed  Google Scholar 

  • Minami M, Yoshikawa H (1979) A simplified assay method of superoxide dismutase activity for clinical use. Clin Chim Acta 92:337–342

    Article  CAS  PubMed  Google Scholar 

  • Misra HP, Fridovich J (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay superoxide dismutase. J Biol Chem 247:3170–3175

    CAS  PubMed  Google Scholar 

  • Moncayo J, de Freitas GR, Bogousslavsky J, Altieri M, van Melle G (2000) Do transient ischemic attacks have a neuroprotective effect? Neurology 54(11):2089–2094

    Article  CAS  PubMed  Google Scholar 

  • Nanetti L, Raffaelli F, Vignini A, Perozzi C, Silvestrini M, Bartolini M et al (2011) Oxidative stress in ischaemic stroke. Eur J Clin Invest 41(12):1318–1322

    Article  CAS  PubMed  Google Scholar 

  • Okado-Matsumoto A, Fridovich I (2001) Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu, Zn-SOD in mitochondria. J Biol Chem 276:38388–38393

    Article  CAS  PubMed  Google Scholar 

  • Ozkul A, Akyol A, Yenisey C, Arpaci E, Kiylioglu N, Tataroglu C (2007) Oxidative stress in acute ischemic stroke. J Clin Neurosci 14:1062–1066

    Article  CAS  PubMed  Google Scholar 

  • Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. Lab Clin Med 70:158–169

    CAS  Google Scholar 

  • Polidori MC, Cherubini A, Stahl W, Senin U, Sies H, Mecocci P (2002) Plasma carotenoid and malondialdehyde levels in ischemic stroke patients: relationship to early outcome. Free Radic Res 36:265–268

    Article  CAS  PubMed  Google Scholar 

  • Sarti C, Rastenyte D, Cepaitis Z, Tuomilehto J (2000) International trends in mortality from stroke, 1968 to 1994. Stroke 31:1588–1601

    Article  CAS  PubMed  Google Scholar 

  • Schaller B, Graf R (2004) Cerebral ischemia and reperfusion: the pathophysiologic concept as a basis for clinical therapy. J Cereb Blood Flow Metab 24:351–371

    Article  PubMed  Google Scholar 

  • Schulz JB, Lindenau J, Seyfried J, Dichgans J (2000) Glutathione, oxidative stress and neurodegeneration. Eur J Biochem 267:4904–4911

    Article  CAS  PubMed  Google Scholar 

  • Sedlak J, Lindsay RH (1968) Estimation of total protein bound and non-protein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205

    Article  CAS  PubMed  Google Scholar 

  • Sheng H, Enghild JJ, Bowler R, Patel M, Batinic-Haberle I, Calvi CL et al (2002) Effects of metalloporphyrin catalytic antioxidants in experimental brain ischemia. Free Radic Biol Med 33(7):947–961

    Article  CAS  PubMed  Google Scholar 

  • Silva DA, Woon FP, Lee MP, Chen CL, Chang HM, Wong MC (2009) Metabolic syndrome is associated with intracranial large artery disease among ethnic Chinese patients with stroke. J Stroke Cerebrovasc Dis 18:424–427

    Article  PubMed  Google Scholar 

  • Sudha K, Rao AV, Rao S, Rao A (2004) Lipid peroxidation, hemolysis and antioxidant enzymes of erythrocytes in stroke. J. Indian. Physiol Pharmacol 48:199–205

    CAS  Google Scholar 

  • Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J et al (1996) Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 49:1304–1313

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the grant from the scientific project number 41018 financed by the Ministry of Education and Science, Republic of Serbia.

Author information

Authors and Affiliations

  1. Faculty of Medicine, University of Nis, Bul. Dr. Zorana Djindjica 81, Nis, 18000, Serbia

    Srdjan Ljubisavljevic, Tatjana Cvetkovic, Svetlana Stojanovic, Ivana Stojanovic, Gordana Kocic, Miroslava Zivkovic & Dusica Pavlovic

  2. Clinic of Neurology, Clinical Center Nis, Bul. Dr. Zorana Djindjica 48, Nis, 18000, Serbia

    Srdjan Ljubisavljevic, Miroslava Zivkovic, Lidija Paunovic, Ljiljana Milenkovic, Dragisa Lukic & Jelena Stamenovic

  3. Center for Clinical Biochemistry, Clinical Center Nis, Bul. Dr. Zorana Djindjica 48, Nis, 18000, Serbia

    Lilika Zvezdanovic

Authors
  1. Srdjan Ljubisavljevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tatjana Cvetkovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lilika Zvezdanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Svetlana Stojanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ivana Stojanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gordana Kocic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Miroslava Zivkovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lidija Paunovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ljiljana Milenkovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Dragisa Lukic
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jelena Stamenovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Dusica Pavlovic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Srdjan Ljubisavljevic.

Ethics declarations

Conflict of interest

No conflict of interest exists for any of the authors listed in the article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ljubisavljevic, S., Cvetkovic, T., Zvezdanovic, L. et al. The Differences in the Cellular and Plasma Antioxidative Capacity Between Transient and Defined Focal Brain Ischemia: Does it Suggest Supporting Time-Dependent Neuroprotection Therapy?. Cell Mol Neurobiol 36, 789–800 (2016). https://doi.org/10.1007/s10571-015-0262-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-015-0262-y

Keywords

Search

Navigation