ÖZ
İnme, dünya genelinde önde gelen ölüm ve kalıcı sakatlık nedenlerinden biridir ve en sık görülen alt tipi iskemik inmedir. Nörogörüntüleme yöntemleri ve reperfüzyon tedavilerindeki önemli ilerlemelere rağmen, hızlı ve doğru tanı klinik uygulamada hala büyük bir güçlük oluşturmaktadır. Astrositlere özgü bir ara filament proteini olan glial fibriller asidik protein, son yıllarda kan temelli umut verici bir biyobelirteç olarak öne çıkmıştır. Astrosit hasarı ve kan-beyin bariyerinin bozulmasını takiben glial fibriller asidik protein ekstrasellüler alana ve dolaşıma salınmaktadır. Hemorajik inmede düzeyler hızla yükselirken, iskemik inmede artış daha yavaş olmakta ve genellikle semptomların başlamasından sonraki ilk 24 ila 48 saat içerisinde ölçülebilir seviyelere ulaşmaktadır. Klinik araştırmalar, iskemik inme hastalarında kanda glial fibriller asidik protein düzeylerinin sağlıklı bireylere kıyasla belirgin şekilde yüksek olduğunu ve bu artışın nörolojik şiddet, enfarktüs hacmi ve fonksiyonel sonuçlarla ilişkili olduğunu göstermiştir. Bu nedenle glial fibriller asidik protein, prognostik öngörüler sunarak hasta sınıflamasına katkıda bulunabilir. Ancak, eşik değerlerdeki değişkenlik, ölçüm yöntemlerindeki farklılıklar ve gecikmiş kinetik önemli sınırlılıklar oluşturmaktadır. Gelecekte glial fibriller asidik proteinin multimarker panellere entegrasyonu ve ultrasensitif hızlı testlerin geliştirilmesi, acil servislerde daha etkin karar süreçlerini mümkün kılabilir. Genel olarak glial fibriller asidik protein, iskemik inmede tanı, prognoz ve izlem için tamamlayıcı bir biyobelirteç olma potansiyeline sahiptir.
Anahtar Kelimeler:
İskemik inme, glial fibriller asidik protein, biyobelirteç, nöroenflamasyon, prognoz
Kaynaklar
1
Feigin VL, Brainin M, Norrving B, Martins SO, Pandian J, Lindsay P, et al. World stroke organization: global stroke fact sheet 2025. Int J Stroke. 2025;20:132-44.
2
GBD 2021 Stroke Risk Factor Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol. 2024;23:973-1003.
3
Makris K, Haliassos A, Chondrogianni M, Tsivgoulis G. Blood biomarkers in ischemic stroke: potential role and challenges in clinical practice and research. Crit Rev Clin Lab Sci. 2018;55:294-328.
4
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. Int J Mol Sci. 2023;24:11545.
5
Markus HS, de Leeuw FE. Cerebral small vessel disease: recent advances and future directions. Int J Stroke. 2023;18:4-14.
6
Atkins ER, Brodie FG, Rafelt SE, Panerai RB, Robinson TG. Dynamic cerebral autoregulation is compromised acutely following mild ischaemic stroke but not transient ischaemic attack. Cerebrovasc Dis. 2010;29:228-35.
7
Lui F, Khan Suheb MZ, Patti L. Ischemic stroke. 2025 Feb 21. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025.
8
Chalet L, Boutelier T, Christen T, Raguenes D, Debatisse J, Eker OF, et al. Clinical imaging of the penumbra in ischemic stroke: from the concept to the era of mechanical thrombectomy. Front Cardiovasc Med. 2022;9:861913.
9
Yan HF, Zou T, Tuo QZ, Xu S, Li H, Belaidi AA, Lei P. Ferroptosis: mechanisms and links with diseases. Signal Transduct Target Ther. 2021;6:49.
10
Jin Y, Zhuang Y, Liu M, Che J, Dong X. Inhibiting ferroptosis: a novel approach for stroke therapeutics. Drug Discov Today. 2021;26:916-30.
11
Wang Q, Yang F, Duo K, Liu Y, Yu J, Wu Q, et al. The role of necroptosis in cerebral ischemic stroke. Mol Neurobiol. 2023;60:1-17.
12
Moltrasio C, Romagnuolo M, Marzano AV. NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: from cryopyrin function to targeted therapies. Front Immunol. 2022;13:1007705.
13
Koehler RC, Dawson VL, Dawson TM. Targeting parthanatos in ischemic stroke. Front Neurol. 2021;12:662034.
14
Mendelson SJ, Prabhakaran S. Diagnosis and management of transient ischemic attack and acute ischemic stroke: a review. JAMA. 2021;325:1088-98.
15
Gao X, Liu D, Yue K, Zhang Z, Jiang X, Luo P. Revolutionizing ischemic stroke diagnosis and treatment: the promising role of neurovascular unit-derived extracellular vesicles. Biomolecules. 2024;14:378.
16
Cabezas JA, Bustamante A, Giannini N, Pecharroman E, Katsanos AH, Tsivgoulis G, et al. Discriminative value of glial fibrillar acidic protein as a diagnostic tool in acute stroke: individual patient data meta-analysis. J Investig Med. 2020;68:1379-85.
17
Patil S, Rossi R, Jabrah D, Doyle K. Detection, diagnosis and treatment of acute ischemic stroke: current and future perspectives. Front Med Technol. 2022;4:748949.
18
Hilkens NA, Casolla B, Leung TW, de Leeuw FE. Stroke. Lancet. 2024;403:2820-36.
19
Feske SK. Ischemic stroke. Am J Med. 2021;134:1457-64.
20
Ho JP, Powers WJ. Contemporary management of acute ischemic stroke. Annu Rev Med. 2025;76:417-29.
21
Saposnik G, Bushnell C, Coutinho JM, Field TS, Furie KL, Galadanci N, et al. Diagnosis and management of cerebral venous thrombosis: a scientific statement from the American Heart Association. Stroke. 2024;55:e77-e90.
22
Berge E, Whiteley W, Audebert H, De Marchis GM, Fonseca AC, Padiglioni C, et al. European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J. 2021;6:I-LXII.
23
Saver JL, Goyal M, van der Lugt A, Menon BK, Majoie CB, Dippel DW, et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA. 2016;316:1279-88.
24
Powers WJ, Derdeyn CP, Biller J, Coffey CS, Hoh BL, Jauch EC, et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ıschemic stroke regarding endovascular treatment: a guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015;46:3020-35.
25
Verkhratsky A, Butt A. Glial physiology and pathophysiology. Wiley. 2013;93-6.
26
Abdelhak A, Foschi M, Abu-Rumeileh S, Yue JK, D’Anna L, Huss A, et al. Blood GFAP as an emerging biomarker in brain and spinal cord disorders. Nat Rev Neurol. 2022;18:158-72.
27
Yang Z, Wang KKK. Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci. 2015;38:364-74.
28
Hase Y, Chen A, Bates LL, Craggs LJL, Yamamoto Y, Gemmell E, et al. Severe white matter astrocytopathy in CADASIL. Brain Pathol. 2018;28:832-43.
29
Petzold A. Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease. Brain Res. 2015;1600:17-31.
30
Abdelhak A, Huss A, Kassubek J, Tumani H, Otto M. Serum GFAP as a biomarker for disease severity in multiple sclerosis. Sci Rep. 2018;8:14798.
31
Tumani H, Huss A, Bachhuber F. The cerebrospinal fluid and barriers: anatomic and physiologic considerations. Handb Clin Neurol. 2017;146:21-32.
32
Petzold A, Lu CH, Groves M, Gobom J, Zetterberg H, Shaw G, et al. Protein aggregate formation permits millennium-old brain preservation. J R Soc Interface. 2020;17:20190775.
33
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;58:237-45.
34
Amalia L. Glial fibrillary acidic protein (GFAP): neuroinflammation biomarker in acute ıschemic stroke. J Inflamm Res. 2021;14:7501-6.
35
Ferrari F, Rossi D, Ricciardi A, Morasso C, Brambilla L, Albasini S, et al. Quantification and prospective evaluation of serum NfL and GFAP as blood-derived biomarkers of outcome in acute ischemic stroke patients. J Cereb Blood Flow Metab. 2023;43:1601-11.
36
Wunderlich MT, Wallesch CW, Goertler M. Release of glial fibrillary acidic protein is related to the neurovascular status in acute ischemic stroke. Eur J Neurol. 2006;13:1118-23.
37
Kalra LP, 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). Eur Stroke J. 2021;6:176-84.
38
van den Bossche WBL, Vincent AJPE, Teodosio C, Koets J, Taha A, Kleijn A, et al. Monocytes carrying GFAP detect glioma, brain metastasis and ischaemic stroke, and predict glioblastoma survival. Brain Commun. 2020;3:fcaa215.
