Serum levels of fibroblast growth factor in patients with intracerebral hemorrhage

Abstract

Objectives: Intracerebral hemorrhage (ICH) is one of the most mortal subtypes of stroke. Due to the angiogenic, neurotropic, and vessel-dilating properties of basic fibroblast growth factor (bFGF) in the brain, role of bFGF has been investigated in a number of neurological disorders. So far, there is only study about serum bFGF levels in patients with ICH. The first aim of the present research is to investigate whether increased serum bFGF in patients with ICH. Also, second aim was to study the association between serum levels of bFGF and clinical status in patients with ICH. Materials and methods: We measured the serum levels of bFGF in 30 patients with ICH during acute period. Age and sex matched healthy subjects (n=30) were included in controls. Serum bFGF levels were measured using an enzyme-linked immunosorbent assay method. Results: The patients with intracerebral hemorrhage had higher serum levels of bFGF when compared with the healthy controls (12.89±3.23 ng/ml, 5.28±1.75 ng/ml; p=0.001). No statistically significant difference was determined between bFGF levels of the patients who died as compared to the patients who lived (13.49±4.13 ng/ml; 12.43±3.43 ng/ml, p>0.05). No statistically significant difference was found between bFGF levels of the patients with intraventricular hemorrhage as compared to the patients without intraventricular hemorrhage (13.54±3.92 ng/ml; 12.24±2.29 ng/ml, p>0.05). There was no correlation between serum bFGF, hematoma volume, Gloskow coma scale, and National Institutes of Health stroke scale (p>0.05). Conclusion: The increased bFGF level may be one of the mechanisms that lead to angiogenesis and neuroprotection after ICH in human.

Keywords

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İntraserebral kanamalı hastalarda serum fibroblast büyüme faktörü düzeyleri

Öz

Amaç: İntraserebral kanama inmenin en ölümcül alt tiplerinden birisidir. Beyinde bazik fibroblast büyüme faktörünün (bFGF) anjiogenik, nörotropik ve damar genişletici özellikleri nedeniyle çok sayıda nörolojik hastalıkta bFGF\'nin rolü araştırılmıştır. Şu ana kadar intraserebral kanamalı hastaların serumunda bFGF\'yi araştıran sadece bir çalışma vardır. Bu çalışmanın birinci amacı intraserebral kanamalı hastaların serumunda bFGF artışı olup olmadığını araştırmaktır. Ayrıca ikinci amacımız intraserebral kanamalı hastalarda serum bFGF ile klinik durumla ilişkisini araştırmaktı. Gereç ve yöntem: Akut dönemde 30 intraserebral kanamalı hastada serum bFGF seviyelerini ölçtük. Yaş ve cinsiyet yönünden benzer 30 sağlıklı kişi kontrol grubuna dahil edildi. ELİSA yöntemiyle serumda bFGF ölçüldü. Bulgular: Serum bFGF seviyeleri intraserebral kanamalı hastalarda (12.89±3.23 ng/ml) kontrol grubuna (5.28±1.75 ng/ml) göre istatistiksel olarak anlamlı düzeyde yüksek bulundu (p=0.001). İntraserebral kanamalı (İSK) hastalarda ölenlerle (n=13) sağ kalanların (n=17) serum bFGF düzeyi benzerdi (13.49±4.13 ng/ml; 12.43±3.43 ng/ml, p>0.05). Ventriküle açılım gösteren (n=15) İSK\'li hastalarla ventriküle açılım göstermeyen (n=15) hastaların bFGF düzeyi arasında fark bulunmadı (13.54±3.92 ng/ml; 12.24±2.29 ng/ml, p>0.05). İntraserebral kanamalı hastalarda serum bFGF düzeyi ile hematom hacmi, Glaskow koma skalası ve uluslar arası inme skalası arasında ilişki bulunmadı (p>0.05). Sonuç: İnsanlarda intraserebral kanamadan sonra artmış bFGF nöron koruyucu ve anjiogeneze neden olan mekanizmalardan birisi olabilir.

Anahtar Kelimeler

• bazik fibroblast büyüme faktörü, intraserebral kanama, anjiogenez

Kaynakça

1. 1. Brown RD, Whisnant JP, Sicks JD, O’Fallon WM, Wiebers DO. Stroke incidence, prevalence, and survival: Secular trends in Rochester, Minnesota, through 1989. Stroke 1996;27(3):373–80.
2. 2. Tang T, Liu XJ, Zhang ZQ, Zhou HJ, Luo JK, Huang JF, Yang QD, Li XQ. Cerebral angiogenesis after collagenase-induced intracerebral hemorrhage in rats. Brain Res 2007;1175(1):134-42.
3. 3. Sobrino T, Arias S, Rodríguez-González R, et al. High serum levels of growth factors are associated with good outcome in intracerebral hemorrhage. J Cereb Blood Flow Metab 2009;29(12):1968-74.
4. 4. Erdem F, Gündoğdu M. Anjiojenesis ve anti-anjiojenik tedavi. AÜTD 2005;37(1): 1-6.
5. 5. Bikfalvi A, Klein S, Pintucci G, Rifkin DB. Biological roles of fibroblast growth factor-2. Endocr Rev 1997;18(1):26– 45.
6. 6. Seghezzi G, Patel S, Ren CJ, Gualandris A, et al. Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries. An autocrine mechanism contributing to angiogenesis. J Cell Biol 1983;141: 1659-73.
7. 7. Przybylski M.A review of the current research on the role of bFGF and VEGF in angiogenesis. J Wound Care 2009;18(12):516-9.
8. 8. Seki T, Abdel Nazeer A, Sekimoto K, Guao Y, Al-jahdari W, Saito S. Fibroblast growth factor and insulin-like growth factor rescue growth cones of sensory neurites from collapse after tetracaine-induced injury. Anesth Analg 2010; 110(5):1468-72.

9. 9. Kawakami N, Kashiwagi S, Kitahara T, Yamashita T, Ito H.Effect of local administration of basic fibroblast growth factor against neuronal damage caused by transient intracerebral mass lesion in rats. Brain Res 1995;697(1-2):104- 11.
10. 10. Lyden P, Brott T, Tilley B, et al. Improved reliability of the NIH Stroke Scale using video training. NINDS TPA Stroke Study Group. Stroke 1994;25(11):2220-6.
11. 11. Kothari RU, Brott T, Broderick JP, et al.The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996;27(8):1304-5.
12. 12. Kawamata T, Speliotas EK, Finklestein SP. The role of polypeptide growth factors in recovery from stroke. Adv Neurol 1997;73:377–82.
13. 13. Issa R, AlQteİSKat A, Mitsios N, et al. Expression of basic fibroblast growth factor mRNA and protein in the human brain following ischaemic stroke. Angiogenesis 2005;8(1):53-62.
14. 14. Slevin M, Krupinski J, Slowik A, Kumar P, Szczudlik A, Gaffney J. Serial measurement of vascular endothelial growth factor and transforming growth factor-beta1 in serum of patients with acute ischemic stroke. Stroke 2000;31(8):1863-70.
15. 15. Gonzales AM, Berry M, Maher PA, Logan A, Baird A. A comprehensive analysis of the distribution of FGF-2 and FGFR1 in the rat brain. Brain Res 1995;701(1-2):201–26.
16. 16. Slavin J. Fibroblast growth factor at the heart of angiogenesis. Cell Biol Int Rep 1995;19(5):431–43.
17. 17. Krupinski J, Kaluza J, Kumar P, Wang M, Kumar S. Prognostic value of blood vessel density in ischaemic stroke. Lancet 1993;342(8873):742-3.
18. 18. Hu HW, Li XK, Zheng RY, Xiao J, Zeng JQ, Hou ST. bFGF expression mediated by a hypoxia-regulated adenoviral vector protects PC12 cell death induced by serum deprivation. Biochem Biophys Res Commun 2009;390(1):115-20.
19. 19. Ma YP, Ma MM, Cheng SM, et al. Intranasal bFGFinduced progenitor cell proliferation and neuroprotection after transient focal cerebral ischemia. Neurosci Lett 2008;437(2):93-7.
20. 20. Li Q, Stephenson D. Postischemic administration of basic fibroblast growth factor improves sensorimotor function and reduces infarct size following permanent focal cerebral ischemia in the rat. Exp Neurol 2002;177(2):531-7.
21. 21. Wang JH, Liu N, Du HW, et al. Effects of adipose-derived stem cell transplantation on the angiogenesis and the expression of bFGF and VEGF in the brain post focal cerebral ischemia in rats. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2008;24(10):958-61.
22. 22. Guo H, Huang L, Cheng M, Jin X, Zhao Y, Yi M. Serial measurement of serum basic fibroblast growth factor in patients with acute cerebral infarction. Neurosci Lett 2006;393(1):56-9.
23. 23. Tanaka R, Miyasaka Y, Yada K, Ohwada T, Kameya T. Basic fibroblast growth factor increases regional cerebral blood flow and reduces infarct size after experimental ischemia in a rat model. Stroke 1995;26(11):2154-8.
24. 24. Ay I, Sugimori H, Finklestein SP. Intravenous basic fibroblast growth factor (bFGF) decreases DNA fragmentation and prevents downregulation of Bcl-2 expression in the ischemic brain following middle cerebral artery occlusion in rats. Brain Res Mol Brain Res 2001;87(1):71-80.
25. 25. Zimering MB, Anderson RJ, Ge L, Moritz TE. Investigators for the VADT. Increased plasma basic fibroblast growth factor is associated with coronary heart disease in adult type 2 diabetes mellitus. Metabolism 2011;60(2):284-91.