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Stability Analysis of Vascular Endothelial Growth Factor in Cerebrospinal Fluid

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Abstract

Vascular endothelial growth factor (VEGF) is a promising biological marker and prognostic indicator in many neurological diseases. Although VEGF concentrations in plasma and cerebrospinal fluid (CSF) are increasingly reported, CSF-VEGF stability pre- and during-assay procedures is seldom evaluated. In the current study, we investigated VEGF variability and stability in CSF related to sample preparation, storage, and routine experimental procedures. Results showed that contaminant cell breakdown or aggregation can occur gradually before sample processing. However, after the removal of contaminant cell components, CSF-VEGF levels did not show significant changes in samples incubated at room temperature for 5 h, thawed/refrozen for 6 cycles. Samples preserved at −80°C for up to 7 years continued to show measurable levels. Since some cellular components such as platelets contain a large amount of releasable VEGF, we conclude that CSF samples should be processed as soon as possible to carefully remove all cellular components and prevent possible consequent release of VEGF into CSF. After centrifugation to remove cellular contents, VEGF in CSF was relatively stable during routine experimental procedures and storage.

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References

  1. Ferrara N (2010) Vascular endothelial growth factor and age-related macular degeneration: from basic science to therapy. Nat Med 16:1107–1111

    Article  PubMed  CAS  Google Scholar 

  2. Ferrara N (1999) Molecular and biological properties of vascular endothelial growth factor. J Mol Med (JMM) 77:527–543

    Article  CAS  Google Scholar 

  3. Ferrara N (1996) Vascular endothelial growth factor. Eur J Cancer 32A:2413–2422

    Article  PubMed  CAS  Google Scholar 

  4. Dombrowski SM, Deshpande A, Dingwall C et al (2008) Chronic hydrocephalus-induced hypoxia: increased expression of VEGFR-2+ and blood vessel density in hippocampus. Neuroscience 152:346–359

    Article  PubMed  CAS  Google Scholar 

  5. Yang J, Dombrowski SM, Deshpande A et al (2010) VEGF/VEGFR-2 changes in frontal cortex, choroid plexus, and CSF after chronic obstructive hydrocephalus. J Neurol Sci 296:39–46

    Article  PubMed  CAS  Google Scholar 

  6. Deshpande A, Dombrowski SM, Leichliter A et al (2009) Dissociation between vascular endothelial growth factor receptor-2 and blood vessel density in the caudate nucleus after chronic hydrocephalus. J Cereb Blood Flow Metab 29:1806–1815

    Article  PubMed  CAS  Google Scholar 

  7. Moreau C, Devos D, Brunaud-Danel V et al (2006) Paradoxical response of VEGF expression to hypoxia in CSF of patients with ALS. J Neurol Neurosurg Psychiatry 77:255–257

    Article  PubMed  CAS  Google Scholar 

  8. Hu WT, Chen-Plotkin A, Arnold SE et al (2010) Novel CSF biomarkers for Alzheimer’s disease and mild cognitive impairment. Acta Neuropathol 119:669–678

    Article  PubMed  CAS  Google Scholar 

  9. Tarnaris A, Toma AK, Chapman MD et al (2009) The longitudinal profile of CSF markers during external lumbar drainage. J Neurol Neurosurg Psychiatry 80:1130–1133

    Article  PubMed  CAS  Google Scholar 

  10. Hormbrey E, Gillespie P, Turner K et al (2002) A critical review of vascular endothelial growth factor (VEGF) analysis in peripheral blood: is the current literature meaningful? Clin Exp Metastas 19:651–663

    Article  CAS  Google Scholar 

  11. Provencio JJ, Kivisakk P, Tucky BH et al (2005) Comparison of ventricular and lumbar cerebrospinal fluid T cells in non-inflammatory neurological disorder (NIND) patients. J Neuroimmunol 163:179–184

    Article  PubMed  CAS  Google Scholar 

  12. Banks RE, Forbes MA, Kinsey SE et al (1998) Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology. Br J Cancer 77:956–964

    Article  PubMed  CAS  Google Scholar 

  13. Maloney JP, Silliman CC, Ambruso DR et al (1998) In vitro release of vascular endothelial growth factor during platelet aggregation. Am J Physiol 275:H1054–H1061

    PubMed  CAS  Google Scholar 

  14. Gunsilius E, Petzer A, Stockhammer G et al (2000) Thrombocytes are the major source for soluble vascular endothelial growth factor in peripheral blood. Oncology 58:169–174

    Article  PubMed  CAS  Google Scholar 

  15. Mohle R, Green D, Moore MA et al (1997) Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc Natl Acad Sci USA 94:663–668

    Article  PubMed  CAS  Google Scholar 

  16. Wartiovaara U, Salven P, Mikkola H et al (1998) Peripheral blood platelets express VEGF-C and VEGF which are released during platelet activation. Thromb Haemost 80:171–175

    PubMed  CAS  Google Scholar 

  17. O’byrne KJ, Dobbs N, Propper D et al (1999) Vascular endothelial growth factor platelet counts, and prognosis in renal cancer. Lancet 353:1494–1495

    Article  PubMed  Google Scholar 

  18. Harris AL (1998) Anti-angiogenesis therapy and strategies for integrating it with adjuvant therapy. Recent Results Cancer Res 152:341–352

    PubMed  CAS  Google Scholar 

  19. Salven P, Teerenhovi L, Joensuu H (1997) A high pretreatment serum vascular endothelial growth factor concentration is associated with poor outcome in non-Hodgkin’s lymphoma. Blood 90:3167–3172

    PubMed  CAS  Google Scholar 

  20. Freeman MR, Schneck FX, Gagnon ML et al (1995) Peripheral blood T lymphocytes and lymphocytes infiltrating human cancers express vascular endothelial growth factor: a potential role for T cells in angiogenesis. Cancer Res 55:4140–4145

    PubMed  CAS  Google Scholar 

  21. Berse B, Brown LF, Van De Water L et al (1992) Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors. Mol Biol Cell 3:211–220

    PubMed  CAS  Google Scholar 

  22. Aursnes I, Vikholm V (1984) On a possible interaction between ADP and mechanical stimulation in platelet activation. Thromb Haemost 51:54–56

    PubMed  CAS  Google Scholar 

  23. Webb NJ, Bottomley MJ, Watson CJ et al (1998) Vascular endothelial growth factor (VEGF) is released from platelets during blood clotting: implications for measurement of circulating VEGF levels in clinical disease. Clin Sci (Lond) 94:395–404

    CAS  Google Scholar 

  24. Reid TJ, Larussa VF, Esteban G et al (1999) Cooling and freezing damage platelet membrane integrity. Cryobiology 38:209–224

    Article  PubMed  CAS  Google Scholar 

  25. Sanz C, Pereira A, Faundez AI et al (1997) Prolonged holding of whole blood at 22 degrees C does not increase activation in platelet concentrates. Vox Sang 72:225–228

    Article  PubMed  CAS  Google Scholar 

  26. Jacobsen J, Rasmuson T, Grankvist K et al (2000) Vascular endothelial growth factor as prognostic factor in renal cell carcinoma. J Urol 163:343–347

    Article  PubMed  CAS  Google Scholar 

  27. Wynendaele W, Derua R, Hoylaerts MF et al (1999) Vascular endothelial growth factor measured in platelet poor plasma allows optimal separation between cancer patients and volunteers: a key to study an angiogenic marker in vivo? Ann Oncol 10:965–971

    Article  PubMed  CAS  Google Scholar 

  28. Salven P, Ruotsalainen T, Mattson K et al (1998) High pre-treatment serum level of vascular endothelial growth factor (VEGF) is associated with poor outcome in small-cell lung cancer. Int J Cancer 79:144–146

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to acknowledge the nursing staffs who work in the neurological ward (H60-61) at the Cleveland Clinic for their help in collecting samples and the team members who work in the Section of Pediatric and Congenital Neurological Surgery at the Cleveland Clinic for their help in clinical data collection.

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Authors and Affiliations

  1. Department of Neurological Surgery, Section of Pediatric and Congenital Neurological Surgery, CSF Physiology Laboratory, Neurological Institute, Cleveland Clinic, S-60, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Jun Yang, Stephen M. Dombrowski, Abhishek Deshpande, Natalie Krajcir, Serge El-Khoury, Chandra Krishnan & Mark G. Luciano

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  1. Jun Yang
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  2. Stephen M. Dombrowski
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  3. Abhishek Deshpande
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  4. Natalie Krajcir
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  5. Serge El-Khoury
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  6. Chandra Krishnan
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  7. Mark G. Luciano
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Correspondence to Mark G. Luciano.

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Yang, J., Dombrowski, S.M., Deshpande, A. et al. Stability Analysis of Vascular Endothelial Growth Factor in Cerebrospinal Fluid. Neurochem Res 36, 1947–1954 (2011). https://doi.org/10.1007/s11064-011-0517-z

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  • DOI: https://doi.org/10.1007/s11064-011-0517-z

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