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Mechanism of neurological deficit improvement through analysis in cerebral artery stenosis, Endothelial Progenitor Cells (EPC), Asymmetric Dimethylarginine (ADMA), Malondialdehyde (MDA), and Superoxide Dismutase (SOD) after balloon angioplasty procedure in ischemic stroke patients

  • Nasrul Musadir ,
  • Soetojo ,
  • Syahrul ,
  • Ketut Sudiana ,
  • Budi Utomo ,
  • Muhammad Hamdan ,
  • Fritz Sumantri Usman ,
  • Siti Pariani ,


Link of Vodeo Abstract:


Backgrounds: Balloon angioplasty is one of the endovascular procedures which aims to open atherosclerotic stenosis or occlusion of the cerebral blood vessels. Balloon angioplasty has been performed on ischemic stroke patients with arteriosclerotic stenosis. However, the procedure's outcomes vary, and no microcellular indicator has become a standard for balloon angioplasty.

Methods: NIHSS examination and Digital Subtraction Angiography (DSA) were performed on 35 ischemic stroke patients. NIHSS examination is used to determine the severity of neurological deficits. At the same time, Digital Subtraction Angiography (DSA) is a diagnostic procedure to determine the location and size of the stenotic lesion in the arteries. Patients underwent several laboratory biomarker analyses, including EPC, ADMA, MDA and SOD, followed by balloon angioplasty. Afterward, repeat the DSA procedure. EPC, ADMA, MDA and SOD were re-analysed seven days later and NIHSS was re-examined thirty days after balloon angioplasty.

Results: Stenosis, EPC (p<0.001), MDA (p=0.001), SOD (p=0.001), and NIHSS (p<0.001) have significant output before and after balloon angioplasty (p<0.001). EPC and SOD significantly correlate with neurological deficits alteration (p<0.05). EPC and SOD have a cut-off value of 50% improvement in neurological deficits. EPC and SOD significantly improve neurological deficit (p=0.008 and p<0.001).

Conclusion: The mechanism of neurological deficit improvement in balloon angioplasty procedure happened through the elevation of EPC and SOD levels. The outcomes of balloon angioplasty could be estimated by measuring the EPC and SOD values as the standard for indicators adjustment to measure clinical progress after balloon angioplasty in ischemic stroke patients.


  1. Coupland AP, Thapar A, Qureshi MI, Jenkins H, Davies AH. The definition of stroke. J R Soc Med. 2017;110(1):9-12.
  2. Alrabghi L, Alnemari R, Aloteebi R, Alshammari H, Ayyad M, Al Ibrahim M, et al. Stroke types and management. Int J Community Med Public Heal. 2018;5(9):3715-3719.
  3. Holmstedt CA, Turan TN, Chimowitz MI. Atherosclerotic intracranial arterial stenosis: risk factors, diagnosis, and treatment. Lancet Neurol. 2013;12(11):1106-1114. d
  4. Barton M, Grüntzig J, Husmann M, Rösch J. Balloon Angioplasty - The Legacy of Andreas Grüntzig, M.D. (1939-1985). Front Cardiovasc Med. 2014;1:15.
  5. Holzer RJ, Gauvreau K, Kreutzer J, Leahy R, Murphy J, Lock JE, et al. Balloon angioplasty and stenting of branch pulmonary arteries: adverse events and procedural characteristics: results of a multi-institutional registry. Circ Cardiovasc Interv. 2011;4(3):287-296.
  6. Schwein A, Georg Y, Lejay A, Nicolini P, Hartung O, Contassot D, et al. Endovascular Treatment for Venous Diseases: Where are the Venous Stents? Methodist Debakey Cardiovasc J. 2018;14(3):208–213.
  7. Morris P. Angioplasty and Stenting of Atherosclerotic Disease. In: Morris P, editor. Practical Neuroangiography. 3rd ed. Philadelphia: Lippincott William & Wilkins; 2013:465–484.
  8. Alexopoulou ENB and E. General Principles of Angioplasty and Stenting. In: Walser RAM· E, editor. Handbook of Angioplasty and Stenting Procedures [Internet]. New York: Springer London Dordrecht Heidelberg New York; 2010:57–71.
  9. Wu CC, Huang PH, Lai CL, Leu HB, Chen JW, Lin SJ. The impact of endothelial progenitor cells on restenosis after percutaneous angioplasty of hemodialysis vascular access. PLoS One. 2014;9(6):1–10.
  10. Liao S, Luo C, Cao B, Hu H, Wang S, Yue H, et al. Endothelial Progenitor Cells for Ischemic Stroke: Update on Basic Research and Application. Stem Cells Int. 2017;2017:2193432.
  11. Li DW, Liu ZQ, Wei J, Liu Y, Hu L Sen. Contribution of endothelial progenitor cells to neovascularization (review). Int J Mol Med. 2012;30(5):1000–1006.
  12. Edwards N, Langford-Smith AWW, Wilkinson FL, Alexander MY. Endothelial progenitor cells: New targets for therapeutics for inflammatory conditions with high cardiovascular risk. Front Med. 2018;5:200.
  13. Chen S, Li N, Deb-Chatterji M, Dong Q, Kielstein JT, Weissenborn K, et al. Asymmetric Dimethyarginine as marker and mediator in Ischemic stroke. Int J Mol Sci. 2012;13(12):15983–16004.
  14. Ye S, Zhou X, Lin J, Chen P. Asymmetric Dimethylarginine Induced Apoptosis and Dysfunction of Endothelial Progenitor Cells: Role of Endoplasmic Reticulum Stress Pathway. Biomed Res Int. 2017;2017:6395601.
  15. Suárez-Cuenca JA, Vera-Gómez E, Hernández-Patricio A, Gutiérrez-Buendía JA, Domínguez-Pérez GA, Robledo-Nolasco R, et al. Relation of Coronary Artery Lumen with Baseline , Post-angioplasty Coronary Circulating Pro-Inflammatory Cytokines in Patients with Coronary Artery Disease. Angiology: Open Access. 2019;7(2):1–4.
  16. Lin CP, Lin FY, Huang PH, Chen YL, Chen WC, Chen HY, et al. Endothelial progenitor cell dysfunction in cardiovascular diseases: Role of reactive oxygen species and inflammation. Biomed Res Int. 2013;2013:845037.
  17. Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J Med. 2018;54(4):287–93.
  18. Fukai T, Ushio-Fukai M. Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal. 2011;15(6):1583-1606.
  19. Elsayed WM, Abdel-Gawad EHA, Mesallam DIA, El-Serafy TS. The relationship between oxidative stress and acute ischemic stroke severity and functional outcome. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery. 2020;56(74):1-6.
  20. Sudiana IK. Hantaran Sinyal Pada Proses Inflamasi. Surabaya: Airlangga University Press. 2017:1–76.
  21. Juni RP, Duckers HJ, Vanhoutte PM, Virmani R, Moens AL. Oxidative stress and pathological changes after coronary artery interventions. J Am Coll Cardiol. 2013;61(14):1471–1481.
  22. Gao M, Yao Q, Liu Y, Sun F, Ma Y, Sun G. Association between mobilization of circulating endothelial progenitor cells and time or degree of injury from angioplasty in patients with exertional angina: A prospective study. Exp Ther Med. 2015;10(2):809–815.
  23. Chang YH, Hwang SK, Kwon OK. Primary Angioplasty for Symptomatic Atherosclerotic Middle Cerebral Artery Stenosis. J Cerebrovasc Endovasc Neurosurg. 2014;16(3):166-174.
  24. Luo J, Wang T, Gao P, Krings T, Jiao L. Endovascular treatment of intracranial atherosclerotic stenosis: Current debates and future prospects. Front Neurol. 2018;9:666.
  25. Karanam LSP, Sharma M, Alurkar A, Baddam SR, Pamidimukkala V, Polavarapu R. Balloon Angioplasty for Intracranial Atherosclerotic Disease: A Multicenter Study. J Vasc Interv Neurol. 2017;9(4):29–34.
  26. Song JK, Cacayorin ED, Campbell MS, Fisher S, Malkoff MD, Alexandrov AV, et al. Intracranial balloon angioplasty of acute terminal internal carotid artery occlusions. Am J Neuroradiol. 2002;23(8):1308–1312.
  27. Nguyen TN, Zaidat OO, Gupta R, Nogueira RG, Tariq N, Kalia JS, et al. Balloon angioplasty for intracranial atherosclerotic disease periprocedural risks and short-term outcomes in a multicenter study. Stroke. 2011;42(1):107–111.
  28. Connors JJ, Wojak JC, Hoppe BH. The technique of endovascular intracranial revascularization. Front Neurol. 2014;5:246.
  29. Norman K, Eriksson M, von Euler M. Sex Differences in Ischemic Stroke Within the Younger Age Group: A Register-Based Study. Front Neurol. 2022;13:793181.
  30. Kadooka K, Hagenbuch N, Anagnostakou V, Valavanis A, Kulcsár Z. Safety and efficacy of balloon angioplasty in symptomatic intracranial stenosis: A systematic review and meta-analysis. J Neuroradiol. 2020;47(1):27–32.
  31. Wabnitz A, Chimowitz M. Angioplasty, stenting and other potential treatments of atherosclerotic stenosis of the intracranial arteries: Past, present and future. J Stroke. 2017;19(3):271–276.
  32. Nordmeyer H, Chapot R, Aycil A, Stracke CP, Wallocha M, Hadisurya MJ, et al. Angioplasty and stenting of intracranial arterial stenosis in perforator-bearing segments: A comparison between the anterior and the posterior circulation. Front Neurol. 2018;9:533.
  33. Ueda T, Takaishi S, Yoshie T, Usuki N, Tatsuno K, Ohtsubo H, et al. Long-term outcome and factors associated with restenosis after combination therapy of balloon angioplasty and stenting for symptomatic intracranial stenosis. BMC Neurol. 2022;22(1):1–11.
  34. Zhang Z, Pu Y, Mi D, Liu L. Cerebral Hemodynamic Evaluation After Cerebral Recanalization Therapy for Acute Ischemic Stroke. Front Neurol. 2019;10:719.
  35. El Amki M, Wegener S. Improving cerebral blood flow after arterial recanalization: A novel therapeutic strategy in stroke. Int J Mol Sci. 2017;18(12):2669.
  36. Vaturi M, Lev EI. Acute stroke and attenuation in endothelial progenitor cells: Cause or effect? Isr Med Assoc J. 2019;21(2):120–121.
  37. Meamar R, Nikyar H, Dehghani L, Talebi M, Dehghani M, Ghasemi M, et al. The role of endothelial progenitor cells in transient ischemic attack patients for future cerebrovascular events. J Res Med Sci. 2016;21(3):1–6.
  38. Sibal L, C Agarwal S, D Home P, H Boger R. The Role of Asymmetric Dimethylarginine (ADMA) in Endothelial Dysfunction and Cardiovascular Disease. Curr Cardiol Rev. 2010;6(2):82–90.
  39. Derkacz A, Protasiewicz M, Porȩba R, Doroszko A, Porȩba M, Antonowicz-Juchniewicz J, et al. Plasma asymmetric dimethylarginine predicts restenosis after coronary angioplasty. Arch Med Sci. 2011;7(3):444–448.
  40. Aygul R, Kotan D, Demirbas F, Ulvi H DO. Plasma Oxidants and Antioxidants in Acute Ischaemic Stroke. J Int Med Res. 2006;34(4):413–418.
  41. Menon B, Ramalingam K, Kumar R. Evaluating the Role of Oxidative Stress in Acute Ischemic Stroke. J Neurosci Rural Pract. 2020;11(1):156–159.
  42. Žitňanová I, Šiarnik P, Kollár B, Chomová M, Pazderová P, Andrezálová L, et al. Oxidative Stress Markers and Their Dynamic Changes in Patients after Acute Ischemic Stroke. Oxid Med Cell Longev. 2016;2016:9761697.
  43. Li W, Yang S. Targeting oxidative stress for the treatment of ischemic stroke: Upstream and downstream therapeutic strategies. Brain Circ. 2016;2(4):153-163.
  44. Shirle R, Ord ENJ, Work LM. Oxidative stress and the use of antioxidants in stroke. Antioxidants. 2014;3(3):472–501.
  45. Huang HF, Guo F, Cao YZ, Shi W, Xia Q. Neuroprotection by manganese superoxide dismutase (mnsod) mimics: Antioxidant effect and oxidative stress regulation in acute experimental stroke. CNS Neurosci Ther. 2012;18(10):811–818.
  46. Bruno A, Saha C, Williams LS. Percent Change on the National Institutes of Health Stroke Scale: A Useful Acute Stroke Outcome Measure. J Stroke Cerebrovasc Dis [Internet]. 2009;18(1):56–59.
  47. Putranto TA, Astoro NW, Rachmad B, Setiawan E, Pramonon A, Djuwita, et al. The safety of modified digital subtraction angiography in RSPAD Gatot Soebroto: a comprehensive outlook. Bali Medical Journal. 2020;9(1):1-5.
  48. Sasmita PK, Setyopranoto I, Wibowo S, Sadewa AH. Correlation between serum S100β protein level with neurological deficit in patients with acute intracerebral hemorrhage. Bali Medical Journal. 2019;8(1):63-68.
  49. Ruspanah I, Hermanto Y, Taihuttu YMJ, Ruspanah A, Adam A, Imron A. Implications of VP-Shunt, Sodium Level, Glucose Level Ratio and Neurologic Deficit as Clinical Outcome Prognostic Factor in Adult Meningitis Tuberculosis with Acute Hydrocephalus in Dr. Hasan Sadikin General Hospital. Bali Medical Journal. 2022;11(2):715-721.

How to Cite

Musadir, N., Soetojo, Syahrul, Sudiana, K., Utomo, B., Muhammad Hamdan, Usman, F. S., & Siti Pariani. (2023). Mechanism of neurological deficit improvement through analysis in cerebral artery stenosis, Endothelial Progenitor Cells (EPC), Asymmetric Dimethylarginine (ADMA), Malondialdehyde (MDA), and Superoxide Dismutase (SOD) after balloon angioplasty procedure in ischemic stroke patients. Bali Medical Journal, 12(2), 1827–1824.