The Diagnostic Potential of Glial Fibrillary Acidic Protein (GFAP) in Acute Stroke Patients
Main Article Content
Abstract
Background: Ischaemic stroke (IS) and hemorrhagic stroke (HS) are considered second leading cause of death and causing great disability. Neuroimaging techniques are primarily used to differentiate between them, however they are not available in all centers and can not be used in some patient
Aim: Identifying blood biomarkers that could be easily measured and could differentiate between IS and HS.
Method: This study was case control study, it was performed on 75 subjects: 50 stroke patients and 25 control subject. Blood samples collected within 24 hours of stroke symptoms. GFAP, IL6, CRP was measured by ELISA technique.
Result: This study found that GFAP is significantly higher in stroke patient compared to control group (p < 0.0001). However, no significant difference was observed between IS and HS. In addition, IS and HS showed significantly higher IL-6 levels compared to control (p < 0.0001). Also it was demonstrated highly significant differences in CRP levels among the groups(p < 0.0001). The area under curve of GFAP for discriminating between IS and HS patients were 0.7385, using a cut-off point of (≥235.26pg/ml) GFAP was able to differentiate between IS and HS with 84.62% and 73.08% sensitivity and specificity, respectively. It was demonstrated that there was no correlation between GFAP and IL6 and CRP.
Conclusion: GFAP has acceptable differentiation ability to differentiate between IS and HS
Article Details
Section
This work is licensed under a Creative Commons Attribution 4.0 International License.
How to Cite
References
1- Sacco RL, Kasner SE, Broderick JP, Caplan LR, Connors JJ, Culebras A, Elkind MS, George MG, Hamdan AD, Higashida RT, Hoh BL. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013 Jul;44(7):2064-89. DOI: https://doi.org/10.1161/STR.0b013e318296aeca
2- Al-Obaidi H, Khidhair Z, Jirjees F, Barakat M, AlSalamat H, Kharaba Z, et al. Factors associated with knowledge and awareness of stroke in the Iraqi population: a cross-sectional study. Frontiers in neurology. 2023;14:1144481. DOI: https://doi.org/10.3389/fneur.2023.1144481
3- Alrabghi L, Alnemari R, Aloteebi R, Alshammari H, Ayyad M, Al Ibrahim M, et al. Stroke types and management. Int J Community Med Public Health. 2018;5(9):3715. DOI: https://doi.org/10.18203/2394-6040.ijcmph20183439
4- Chugh C. Acute ischemic stroke: management approach. Indian journal of critical care medicine: peer-reviewed, official publication of Indian Society of Critical Care Medicine. 2019;23(Suppl 2):S140. DOI: https://doi.org/10.5005/jp-journals-10071-23192
5- Bookstaver PB, Chisholm-Burns MA, Kolesar JM, Lee KC, Malone PM, Schwinghammer TL. Pharmacotherapy Principles & Practice: McGraw-Hill Education; 2019.
6- Kuriakose D, Xiao Z. Pathophysiology and treatment of stroke: present status and future perspectives. International journal of molecular sciences. 2020;21(20):7609. DOI: https://doi.org/10.3390/ijms21207609
7- Alawneh KZ, Al Qawasmeh M, Raffee LA, Abuzayed B, Hani DAB, Abdalla KM, et al. A snapshot of Ischemic stroke risk factors, sub-types, and its epidemiology: Cohort study. Annals of Medicine and Surgery. 2020;59:101-5. DOI: https://doi.org/10.1016/j.amsu.2020.09.016
8- Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344-e418. DOI: https://doi.org/10.1161/STR.0000000000000211
9- Patil S, Rossi R, Jabrah D, Doyle K. Detection, diagnosis and treatment of acute ischemic stroke: current and future perspectives. Frontiers in medical technology. 2022;4:748949. DOI: https://doi.org/10.3389/fmedt.2022.748949
10- Wang Y, Su X, Leung GHD, Ren B, Zhang Q, Xiong Z, et al. Circulating microRNAs as diagnostic biomarkers for ischemic stroke: evidence from comprehensive analysis and real-world validation. International journal of medical sciences. 2023;20(8):1009. DOI: https://doi.org/10.7150/ijms.83963
11- Sun B, Wang Z. A Short Review on Advances in Early Diagnosis and Treatment of Ischemic Stroke. Galen medical journal. 2023;12:e2993. DOI: https://doi.org/10.31661/gmj.v12i.2993
12- Li D, Liu X, Liu T, Liu H, Tong L, Jia S, et al. Neurochemical regulation of the expression and function of glial fibrillary acidic protein in astrocytes. Glia. 2020;68(5):878-97. DOI: https://doi.org/10.1002/glia.23734
13- Patabendige A, Singh A, Jenkins S, Sen J, Chen R. Astrocyte activation in neurovascular damage and repair following ischaemic stroke. International journal of molecular sciences. 2021;22(8):4280. DOI: https://doi.org/10.3390/ijms22084280
14- Amalia L. Glial fibrillary acidic protein (GFAP): Neuroinflammation biomarker in acute ischemic stroke. Journal of Inflammation Research. 2021:7501-6. DOI: https://doi.org/10.2147/JIR.S342097
15- Perry LA, Lucarelli T, Penny-Dimri JC, McInnes MD, Mondello S, Bustamante A, et al. Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage: systematic review and meta-analysis of diagnostic test accuracy. International journal of stroke. 2019;14(4):390-9. DOI: https://doi.org/10.1177/1747493018806167
16- di Biase L, Bonura A, Pecoraro PM, Carbone SP, Di Lazzaro V. Unlocking the potential of stroke blood biomarkers: early diagnosis, ischemic vs. haemorrhagic differentiation and haemorrhagic transformation risk: a comprehensive review. International Journal of Molecular Sciences. 2023;24(14):11545. DOI: https://doi.org/10.3390/ijms241411545
17- Hashim NW, Kadhim KA, Rahmah AM. Effect of human insulin and insulin analogue on some inflammatory markers and total antioxidant capacity in a sample of Iraqi type 1 diabetic children and adolescents. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2021;21(2):9-14. DOI: https://doi.org/10.32947/ajps.v21i2.804
18- Ateyah MA, Abdulridha MK, Alkabee MJ. Effects of Saw Palmetto Therapy on some Inflammatory Biomarkers in a Sample of Iraqi Male with Symptomatic Benign Prostatic Hyperplasia. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2021;21(1):1-9. DOI: https://doi.org/10.32947/ajps.v21i1.774
19- Said EA, Al-Reesi I, Al-Shizawi N, Jaju S, Al-Balushi MS, Koh CY, et al. Defining IL-6 levels in healthy individuals: A meta-analysis. Journal of medical virology. 2021;93(6):3915-24. DOI: https://doi.org/10.1002/jmv.26654
20- Babić A, Bonifačić D, Komen V, Kovačić S, Mamić M, Vuletić V. Blood Biomarkers in Ischemic Stroke Diagnostics and Treatment—Future Perspectives. Medicina. 2025;61(3):514. DOI: https://doi.org/10.3390/medicina61030514
21- Dotiwala AK, McCausland C, Samra NS. Anatomy, Head and Neck: Blood Brain Barrier. In: StatPearls. Treasure Island (FL): StatPearls Publishing; April 4, 2023.
22- Kamtchum-Tatuene J, Jickling GC. Blood Biomarkers for Stroke Diagnosis and Management. Neuromolecular medicine. 2019;21(4):344-68. DOI: https://doi.org/10.1007/s12017-019-08530-0
23- Paul JF, Ducroux C, Correia P, Daigneault A, Larochelle C, Stapf C, et al. Serum glial fibrillary acidic protein in acute stroke: feasibility to determine stroke-type, timeline and tissue-impact. Frontiers in Neurology. 2024;Volume 15 - 2024. DOI: https://doi.org/10.3389/fneur.2024.1470718
24- Bhatia R, Warrier AR, Sreenivas V, Bali P, Sisodia P, Gupta A, et al. Role of blood biomarkers in differentiating ischemic stroke and intracerebral hemorrhage. Neurology India. 2020;68(4):824-9. DOI: https://doi.org/10.4103/0028-3886.293467
25- Bustamante A, Penalba A, Orset C, Azurmendi L, Llombart V, Simats A, et al. Blood Biomarkers to Differentiate Ischemic and Hemorrhagic Strokes. Neurology. 2021;96(15):e1928-e39. DOI: https://doi.org/10.1212/WNL.0000000000011742
26- Katsanos AH, Makris K, Stefani D, Koniari K, Gialouri E, Lelekis M, et al. Plasma Glial Fibrillary Acidic Protein in the Differential Diagnosis of Intracerebral Hemorrhage. Stroke. 2017;48(9):2586-8. DOI: https://doi.org/10.1161/STROKEAHA.117.018409
27- Luger S, Witsch J, Dietz A, Hamann GF, Minnerup J, Schneider H, et al. Glial Fibrillary Acidic Protein Serum Levels Distinguish between Intracerebral Hemorrhage and Cerebral Ischemia in the Early Phase of Stroke. Clinical Chemistry. 2017;63(1):377-85. DOI: https://doi.org/10.1373/clinchem.2016.263335
28- Kalra L-P, Khatter H, Ramanathan S, Sapehia S, Devi K, Kaliyaperumal A, et al. Serum GFAP for stroke diagnosis in regions with limited access to brain imaging (BE FAST India). European stroke journal. 2021;6(2):176-84. DOI: https://doi.org/10.1177/23969873211010069
29- Kowalski RG, Ledreux A, Violette JE, Neumann RT, Ornelas D, Yu X, et al. Rapid activation of neuroinflammation in stroke: Plasma and extracellular vesicles obtained on a mobile stroke unit. Stroke. 2023;54(3):e52-e7. DOI: https://doi.org/10.1161/STROKEAHA.122.041422
30- Aref HMA, Fahmy NA, Khalil SH, Ahmed MF, ElSadek A, Abdulghani MO. Role of interleukin-6 in ischemic stroke outcome. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery. 2020;56(1):12. DOI: https://doi.org/10.1186/s41983-019-0121-8
31- Rocco A, Ringleb PA, Grittner U, Nolte CH, Schneider A, Nagel S. Follow-up C-reactive protein level is more strongly associated with outcome in stroke patients than admission levels. Neurological sciences. 2015;36(12):2235-41. DOI: https://doi.org/10.1007/s10072-015-2342-7
32- Băcilă C-I, Vlădoiu M-G, Văleanu M, Moga D-F-C, Pumnea P-M. The Role of IL-6 and TNF-Alpha Biomarkers in Predicting Disability Outcomes in Acute Ischemic Stroke Patients. Life. 2025;15(1):47. DOI: https://doi.org/10.3390/life15010047
33- Retnoningrum D, Wati AP, Rahmawati MB, Ningrum FH, Kuntjoro L, Limijadi EKS. The correlation between c-reactive protein, vascular cell adhesion molecule-1, and s100b with alberta stroke program early ct score in non-hemorrhagic stroke patients. Bali Med J. 2021;10(1):377-81. DOI: https://doi.org/10.15562/bmj.v10i1.2192
34- Shan W, Zhao J, Qiu C, Xu G, Feng J. Glial Fibrillary Acidic Protein Levels in Post-Stroke Depression: A Prospective Ischemic Stroke Cohort. Neuropsychiatric disease and treatment. 2023;19:2171-8. DOI: https://doi.org/10.2147/NDT.S435006
35- Foerch C, Niessner M, Back T, Bauerle M, De Marchis GM, Ferbert A, et al. Diagnostic accuracy of plasma glial fibrillary acidic protein for differentiating intracerebral hemorrhage and cerebral ischemia in patients with symptoms of acute stroke. Clin Chem. 2012;58(1):237-45. DOI: https://doi.org/10.1373/clinchem.2011.172676
36- Ren C, Kobeissy F, Alawieh A, Li N, Li N, Zibara K, et al. Assessment of Serum UCH-L1 and GFAP in Acute Stroke Patients. Scientific reports. 2016;6:24588. DOI: https://doi.org/10.1038/srep24588
37- Traub J, Otto M, Sell R, Homola GA, Steinacker P, Oeckl P, et al. Serum glial fibrillary acidic protein indicates memory impairment in patients with chronic heart failure. ESC heart failure. 2022;9(4):2626-34. DOI: https://doi.org/10.1002/ehf2.13986