Serum vascular endothelial growth factor (VEGF) levels and neuroimaging markers in acute ischemic stroke: A cross-sectional analysis of hounsfield units, infarct volume, and clinical severity

Serum vascular endothelial growth factor (VEGF) levels and neuroimaging markers in acute ischemic stroke: A cross-sectional analysis of hounsfield units, infarct volume, and clinical severity

Authors

  • Jeili Angle Worang Department of Neurology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
  • Muhammad Yunus Amran Division of Interventional Neurology and Neuroendovascular Therapy, Department of Neurology, Faculty of Medicine, Hasanuddin University; Brain Centre, Dr. Wahidin Sudirohusodo General Hospital; Hasanuddin University Teaching Hospital, Makassar, Indonesia https://orcid.org/0000-0001-5079-7490
  • Dwi Atmaji Norwanto Department of Neurology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
  • Muhammad Ikbal Department of Neurology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
  • Muhammad Akbar Department of Neurology, Faculty of Medicine, Hasanuddin University; Brain Centre, Dr. Wahidin Sudirohusodo General Hospital; Hasanuddin University Teaching Hospital, Makassar, Indonesia
  • Gita Vita Soraya Department of Biochemistry, Faculty of Medicine, Hasanuddin University; and Hasanuddin University Teaching Hospital, Makassar, Indonesia
  • Cahyono Kaelan Departement of Anatomy Pathology, Faculty of Medicine, Hasanuddin University; and Hasanuddin University Teaching Hospital, Makassar, Indonesia
  • Citra Rosyidah Department of Physiology, Faculty of Medicine, Hasanuddin University; and Hasanuddin University Teaching Hospital, Makassar, Indonesia

Keywords:

Acute ischemic stroke, biomarker, blood brain barrier, hounsfield unit, infarct volume, NIHSS, vascular endothelial growth factor

Abstract

Background and aim: Vascular Endothelial Growth Factor (VEGF) is a key mediator of angiogenesis, neurogenesis, and blood–brain barrier (BBB) regulation in acute ischemic stroke (AIS). While elevated VEGF may represent a compensatory response, excessive expression can exacerbate tissue injury and cerebral edema. This study investigated the relationship between serum VEGF levels, Hounsfield units (HU), infarct volume, and neurological severity using the National Institutes of Health Stroke Scale (NIHSS).

Methods: This observational, analytical, cross-sectional study was conducted at Dr. Wahidin Sudirohusodo Hospital and affiliated teaching hospitals in Makassar, Indonesia, from September 2025 until sample completion. Thirty-two AIS patients aged 18–65 years, with symptom onset <7 days, were included. Serum VEGF was measured using ELISA, HU values using region-of-interest (ROI) analysis, and infarct volume with the Broderick ABC/2 method on non-contrast CT. Demographics, vascular risk factors, stroke onset, and NIHSS were recorded at admission. Correlations were assessed with Spearman’s rho; p < 0.05 was considered significant.

Results: The mean age was 56.7 ± 8.8 years, with 59.4% male. Most patients presented on day 1 (50%). Common risk factors were dyslipidemia (87.5%), hypertension (68.8%), and smoking (40.6%). Median values were VEGF 213 pg/ml, HU 19, infarct volume 15.4 cm³, and NIHSS 7. VEGF showed a moderate negative correlation with HU (r = –0.419, p = 0.016), a moderate positive correlation with infarct volume (r = 0.447, p = 0.010), and a weak positive correlation with NIHSS (r = 0.358, p = 0.044).

Conclusions: Higher VEGF levels are associated with larger infarct volumes and lower HU values, suggesting greater tissue damage and BBB disruption. The weak correlation with severity highlights the influence of lesion site, collateral flow, and compensatory responses. VEGF may serve as a biomarker for tissue injury progression, supporting integrated imaging and clinical evaluation in early AIS management.

Author Biographies

Jeili Angle Worang, Department of Neurology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

Department of Neurology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

Muhammad Yunus Amran, Division of Interventional Neurology and Neuroendovascular Therapy, Department of Neurology, Faculty of Medicine, Hasanuddin University; Brain Centre, Dr. Wahidin Sudirohusodo General Hospital; Hasanuddin University Teaching Hospital, Makassar, Indonesia

Division of Interventional Neurology and Neuroendovascular Therapy, Department of  Neurology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
Brain Centre, Dr. Wahidin Sudirohusodo General Hospital, Makassar, Indonesia
Hasanuddin University Teaching Hospital, Makassar, Indonesia

Dwi Atmaji Norwanto, Department of Neurology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

Department of Neurology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

Muhammad Ikbal, Department of Neurology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

Department of Neurology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

Muhammad Akbar, Department of Neurology, Faculty of Medicine, Hasanuddin University; Brain Centre, Dr. Wahidin Sudirohusodo General Hospital; Hasanuddin University Teaching Hospital, Makassar, Indonesia

Department of Neurology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
Brain Centre, Dr. Wahidin Sudirohusodo General Hospital, Makassar, Indonesia
Hasanuddin University Teaching Hospital, Makassar, Indonesia

Gita Vita Soraya, Department of Biochemistry, Faculty of Medicine, Hasanuddin University; and Hasanuddin University Teaching Hospital, Makassar, Indonesia

Department of Biochemistry, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
Hasanuddin University Teaching Hospital, Makassar, Indonesia

Cahyono Kaelan, Departement of Anatomy Pathology, Faculty of Medicine, Hasanuddin University; and Hasanuddin University Teaching Hospital, Makassar, Indonesia

Departement of Anatomy Pathology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
Hasanuddin University Teaching Hospital, Makassar, Indonesia

Citra Rosyidah, Department of Physiology, Faculty of Medicine, Hasanuddin University; and Hasanuddin University Teaching Hospital, Makassar, Indonesia

Department of Physiology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
Hasanuddin University Teaching Hospital, Makassar, Indonesia

References

1. Wafa HA, Wolfe CDA, Emmett E, Roth GA, Johnson CO, Wang Y. Burden of Stroke in Europe: Thirty-Year Projections of Incidence, Prevalence, Deaths, and Disability-Adjusted Life Years. Stroke. 2020;51(8):2418-2427. doi:10.1161/STROKEAHA.120.029606

2. Karantali E, Kazis D, Chalikias G, Kasimis D, Tziomalos K, Giannopoulos S. Serum BDNF levels in acute stroke: a systematic review and meta-analysis. Medicina (Kaunas). 2021;57(3):297. doi:10.3390/medicina57030297

3. Setyopranoto I, Bayuangga HF, Panggabean AS, et al. Prevalence of Stroke and Associated Risk Factors in Sleman District of Yogyakarta Special Region, Indonesia. Stroke Res Treat. 2019;2019:2642458. Published 2019 May 2. doi:10.1155/2019/2642458

4. Venketasubramanian N, Yudiarto FL, Tugasworo D. Stroke Burden and Stroke Services in Indonesia. Cerebrovasc Dis Extra. 2022;12(1):53-57. doi:10.1159/000524161

5. Campbell BCV, De Silva DA, Macleod MR, et al. Ischaemic stroke. Nat Rev Dis Primers. 2019;5(1):70. Published 2019 Oct 10. doi:10.1038/s41572-019-0118-8

6. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46-e110. doi:10.1161/STR.0000000000000158

7. Shen F, Walker EJ, Jiang L, et al. Coexpression of angiopoietin-1 with VEGF increases the structural integrity of the blood-brain barrier and reduces atrophy volume. J Cereb Blood Flow Metab. 2011;31(12):2343-2351. doi:10.1038/jcbfm.2011.97

8. Lee SC, Lee KY, Kim YJ, Kim SH, Koh SH, Lee YJ. Serum VEGF levels in acute ischaemic strokes are correlated with long-term prognosis. Eur J Neurol. 2010;17(1):45-51. doi:10.1111/j.1468-1331.2009.02731.x

9. Hu Y, Huang S, Shen T, et al. Prognostic Significance of Plasma VEGFA and VEGFR2 in Acute Ischemic Stroke-a Prospective Cohort Study. Mol Neurobiol. 2024;61(9):6341-6353. doi:10.1007/s12035-024-03973-4

10. Mühl-Benninghaus R, Dressler J, Haußmann A, Simgen A, Reith W, Yilmaz U. Utility of Hounsfield unit in the diagnosis of tandem occlusion in acute ischemic stroke. Neurol Sci. 2021;42(6):2391-2396. doi:10.1007/s10072-020-04798-4

11. Zhu Z, Zhang R, Ren K, et al. The prognosis prediction significance of Hounsfield unit value for stroke patients treated by intravenous thrombolysis. BMC Med Imaging. 2021;21(1):62. Published 2021 Apr 7. doi:10.1186/s12880-021-00592-6

12. Bhasin A, Srivastava MVP, Vivekanandhan S, et al. Vascular Endothelial Growth Factor as Predictive Biomarker for Stroke Severity and Outcome; An Evaluation of a New Clinical Module in Acute Ischemic Stroke. Neurol India. 2019;67(5):1280-1285. doi:10.4103/0028-3886.271241

13. Akbar M, Misbach J, Susatia F, Rasyid A, Alfa AY, Syamsudin T, et al. Clinical features of transient ischemic attack or ischemic stroke patients at high recurrence risk in Indonesia. Neurol Asia. 2018;23(2):107-13

14. Soliman RH, Oraby MI, Fathy M, Essam AM. Risk factors of acute ischemic stroke in patients presented to Beni-Suef University Hospital: prevalence and relation to stroke severity at presentation. Egypt J Neurol Psychiatr Neurosurg. 2018;54(1):8. doi:10.1186/s41983-018-0012-4

15. Harriott AM, Karakaya F, Ayata C. Headache after ischemic stroke: A systematic review and meta-analysis. Neurology. 2020;94(1):e75-e86. doi:10.1212/WNL.0000000000008591

16. El Tallawy HN, Farghaly WM, Badry R, et al. Epidemiology and clinical presentation of stroke in Upper Egypt (desert area). Neuropsychiatr Dis Treat. 2015;11:2177-2183. Published 2015 Aug 21. doi:10.2147/NDT.S87381

17. Govind AS, Sukumar S, Dkhar W. Grading of cerebral infarction using CT-Hounsfield unit in acute, subacute and chronic stroke. Int J Curr Res. 2015;7(7):17874-8. Available from: https://www.journalcra.com/

18. Bier G, Bongers MN, Ditt H, Bender B, Ernemann U, Horger M. Accuracy of Non-Enhanced CT in Detecting Early Ischemic Edema Using Frequency Selective Non-Linear Blending. PLoS One. 2016;11(1):e0147378. Published 2016 Jan 25. doi:10.1371/journal.pone.0147378

19. Hu Y, Zheng Y, Wang T, Jiao L, Luo Y. VEGF, a Key Factor for Blood Brain Barrier Injury After Cerebral Ischemic Stroke. Aging Dis. 2022;13(3):647-654. Published 2022 Jun 1. doi:10.14336/AD.2021.1121

20. Reitmeir R, Kilic E, Reinboth BS, et al. Vascular endothelial growth factor induces contralesional corticobulbar plasticity and functional neurological recovery in the ischemic brain. Acta Neuropathol. 2012;123(2):273-284. doi:10.1007/s00401-011-0914-z

21. Valable S, Montaner J, Bellail A, et al. VEGF-induced BBB permeability is associated with an MMP-9 activity increase in cerebral ischemia: both effects decreased by Ang-1. J Cereb Blood Flow Metab. 2005;25(11):1491-1504. doi:10.1038/sj.jcbfm.9600148

22. Zhang ZG, Zhang L, Jiang Q, et al. VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest. 2000;106(7):829-838. doi:10.1172/JCI9369

23. Greenberg DA, Jin K. Vascular endothelial growth factors (VEGFs) and stroke. Cell Mol Life Sci. 2013;70(10):1753-1761. doi:10.1007/s00018-013-1282-8

24. Fakhri MF. Relationship between serum vascular endothelial growth factor (VEGF) levels, Alberta Stroke Program Early CT Score (ASPECTS), and ischemic stroke subtype in patients with acute middle cerebral artery (MCA) territory ischemic stroke [thesis]. Makassar (ID): Universitas Hasanuddin; 2023. Available from: https://repository.unhas.ac.id/id/eprint/38247/

25. Prodjohardjono A, Vidyanti AN, Susianti NA, Sudarmanta, Sutarni S, Setyopranoto I. Higher level of acute serum VEGF and larger infarct volume are more frequently associated with post-stroke cognitive impairment. PLoS One. 2020;15(10):e0239370. Published 2020 Oct 5. doi:10.1371/journal.pone.0239370

26. Menet R, Nasrallah L, Bernard M, Allain AS, ElAli A. VEGF-E Attenuates Injury After Ischemic Stroke by Promoting Reparative Revascularization. Eur J Neurosci. 2025;61(8):e70114. doi:10.1111/ejn.70114

27. Puspitasari V, Nurkhasanah, Karyono, Hidayat T, Budiono A, Lestari A, et al. Serum vascular endothelial growth factor as a predictor of clinical outcomes in anterior circulation ischemic stroke. Med J Indones. 2015;24(2):109-14. doi:10.13181/mji.v24i2.1196

28. Babkina AS, Yadgarov MY, Ostrova IV, et al. Serum Levels of VEGF-A and Its Receptors in Patients in Different Phases of Hemorrhagic and Ischemic Strokes. Curr Issues Mol Biol. 2022;44(10):4888-4901. Published 2022 Oct 14. doi:10.3390/cimb44100332

29. Moxon JV, Kraeuter AK, Phie J, et al. Serum angiopoietin-1 concentration does not distinguish patients with ischaemic stroke from those presenting to hospital with ischaemic stroke mimics. BMC Cardiovasc Disord. 2022;22(1):462. Published 2022 Nov 4. doi:10.1186/s12872-022-02918-w

30. Matsuo R, Ago T, Kamouchi M, et al. Clinical significance of plasma VEGF value in ischemic stroke - research for biomarkers in ischemic stroke (REBIOS) study. BMC Neurol. 2013;13:32. Published 2013 Apr 8. doi:10.1186/1471-2377-13-32

31. Tian Y, Niu HT, Li MH, Wang YZ. Effect of VEGF on neurological impairment and prognosis of acute cerebral infarction patients: A retrospective case-control study. Medicine (Baltimore). 2023;102(6):e29835. doi:10.1097/MD.0000000000029835

32. Tiedt S, Buchan AM, Dichgans M, Lizasoain I, Moro MA, Lo EH. The neurovascular unit and systemic biology in stroke - implications for translation and treatment. Nat Rev Neurol. 2022;18(10):597-612. doi:10.1038/s41582-022-00703-z

33. Candelario-Jalil E, Dijkhuizen RM, Magnus T. Neuroinflammation, Stroke, Blood-Brain Barrier Dysfunction, and Imaging Modalities. Stroke. 2022;53(5):1473-1486. doi:10.1161/STROKEAHA.122.036946

Downloads

Published

28-10-2025

Issue

Section

ORIGINAL CLINICAL RESEARCH

How to Cite

1.
Worang JA, Amran MY, Norwanto DA, et al. Serum vascular endothelial growth factor (VEGF) levels and neuroimaging markers in acute ischemic stroke: A cross-sectional analysis of hounsfield units, infarct volume, and clinical severity. Acta Biomed. 2025;96(5):17979. doi:10.23750/abm.v96i5.17979