Biomarkers and Vasospasm After Aneurysmal Subarachnoid Hemorrhage

https://doi.org/10.1016/j.nec.2009.10.009Get rights and content

Section snippets

Basics of the human proteome

Human proteomics is the study of human proteins in the context of three realms: drug discovery, proteome mapping, and biologic understanding.17 A number of new scientific techniques have been developed that allow for the identification of proteins from a number of human biologic tissues.18 This material, usually collected in a specific clinical context, gives researchers a glimpse of the activity occurring as the direct result of disease. The study of proteomics in vasospasm and DIND could

Tissue sampling

During the treatment of aneurysmal SAH, various parenchymal sites can be harvested for proteomic analysis. These include solid tissue, such as brain parenchyma; tissue approximating the vascular substructure, such as adventitia; and sections of vessel affected by aneurysmal rupture. Each of these tissue types requires sacrifice in the setting of surgical intervention and is rarely obtained in normal practice. More commonly acquired and easily accessible tissue types include blood, CSF, and

Protein isolation

The first stage of proteome analysis requires the isolation of individual proteins. The most commonly applied technique for protein isolation is two-dimensional gel electrophoresis. This technique uses a two-stage process, including pH immobilization with isoelectric focusing, followed by standard polyacrylamide gel electrophoresis. The proteins can then be visualized using special stains or immunoblotting techniques. Other important protein isolation technologies include affinity

Protein identification

The time and effort required to identify proteins are determined in part by the abundance of the target of interest, as well as its purity, size, and stability during the purification process. The most commonly employed technique for definitive protein identification is mass spectrometry. Mass spectrometry employs protein ionization technology to produce ionized peptide fragments, from which mass-to-charge ratios are determined. Proteins are first eluted from a reversed phase column and then

Biomarkers and mechanistic approaches to vasospasm

The search for biomarkers in SAH and vasospasm has been proceeding for decades. A remarkably large literature focused on the analysis of biomarkers in the context of human tissue and SAH has been developed. At different times various techniques and theoretical perspectives have been employed. Each approach has been based on a theoretical understanding as to the underlying mechanisms of vasospasm. Different approaches have evolved with developments in molecular biology. The first and perhaps

Recent observations

Recent advances in proteomics have yielded the discovery of new proteins that act as markers of brain injury in the setting of SAH and vasospasm. These approaches have identified new protein candidates and have aided in elucidating the molecular basis for vasospasm induced by SAH. Furthermore, these findings may provide new potential targets for the development of therapeutics and interventions aimed at preventing vasospasm. Research has focused on molecules that are markers for damage to

Summary

Proteomics now offers an array of advanced technologies that enable the identification of small quantities of proteins from small samples. As these technologies are further developed, a major challenge will be to address the issue of dynamic variability. Other important factors hampering protein identification are the limitations of techniques for the sequestration and concentration of proteins of interest. Such techniques as two-dimensional gel electrophoresis and chromatography of all types

First page preview

First page preview
Click to open first page preview

References (80)

  • A.G. Kolias et al.

    Pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage: putative mechanisms and novel approaches

    J Neurosci Res

    (2009)
  • J.W. Hop et al.

    Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review [review]

    Stroke

    (1997)
  • R.A. Armonda et al.

    Wartime traumatic cerebral vasospasm: recent review of combat casualties

    Neurosurgery

    (2006)
  • M.N. Diringer

    Management of aneurysmal subarachnoid hemorrhage [review]

    Crit Care Med

    (2009)
  • N.J. Solenski

    Medical complications of aneurysmal subarachnoid hemorrhage: a report of the multicenter, cooperative aneurysm study. Participants of the Multicenter Cooperative Aneurysm Study

    Crit Care Med

    (1995)
  • N.W. Dorsch

    Cerebral arterial spasm—a clinical review

    Br J Neurosurg

    (1995)
  • A. Hijdra

    Delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: clinicoanatomic correlations

    Neurology

    (1986)
  • Y. Hirashima

    The use of computed tomography in the prediction of delayed cerebral infarction following acute aneurysm surgery for subarachnoid haemorrhage

    Acta Neurochir (Wien)

    (1995)
  • A. Forssell

    CT assessment of subarachnoid haemorrhage. A comparison between different CT methods of grading subarachnoid haemorrhage

    Br J Neurosurg

    (1995)
  • A.A. Rabinstein

    Patterns of cerebral infarction in aneurysmal subarachnoid hemorrhage

    Stroke

    (2005)
  • J. Zambranski et al.

    Cerebral vasospams

  • J.I. Suarez et al.

    Aneurysmal subarachnoid hemorrhage

    N Engl J Med

    (2006)
  • R.L. Macdonald

    Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial

    Stroke

    (2008)
  • M. Zwienenberg-Lee

    Effect of prophylactic transluminal balloon angioplasty on cerebral vasospasm and outcome in patients with Fisher grade III subarachnoid hemorrhage: results of a phase II multicenter, randomized, clinical trial

    Stroke

    (2008)
  • E.C. Haley et al.

    A randomized trial of nicardipine in subarachnoid hemorrhage: angiographic and transcranial Doppler ultrasound results. A report of the Cooperative Aneurysm Study

    J Neurosurg

    (1993)
  • F.L. Moseley

    The use of proteomics to identify novel therapeutic targets for the treatment of disease

    J Pharm Pharmacol

    (2007)
  • H.J. Issaq et al.

    Serum and plasma proteomics

    Chem Rev

    (2007)
  • C. Hoogland

    The 1999 SWISS-2DPAGE database update

    Nucleic Acids Res

    (2000)
  • A. Bairoch

    The Universal Protein Resource (UniProt)

    Nucleic Acids Res

    (2005)
  • R.D. Appel et al.

    Post-translational modifications: a challenge for proteomics and bioinformatics

    Proteomics

    (2004)
  • H. Steen et al.

    The ABC's (and XYZ's) of peptide sequencing

    Nat Rev Mol Cell Biol

    (2004)
  • M. Ramstrom

    Cerebrospinal fluid protein patterns in neurodegenerative disease revealed by liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry

    Proteomics

    (2004)
  • J. Bergquist

    Peptide mapping of proteins in human body fluids using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry

    Mass Spectrom Rev

    (2002)
  • M. Merchant et al.

    Recent advancements in surface-enhanced laser desorption/ionization-time of flight-mass spectrometry

    Electrophoresis

    (2000)
  • R.M. Lequin

    Enzyme immunoassay (EIA)/enzyme-linked immunosorbent assay (ELISA)

    Clin Chem

    (2005)
  • K. Lawlor et al.

    Pathway-based biomarker search by high-throughput proteomics profiling of secretomes

    J Proteome Res

    (2009)
  • G. MacBeath et al.

    Printing proteins as microarrays for high-throughput function determination

    Science

    (2000)
  • M.J. McGirt

    Leukocytosis as an independent risk factor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage

    J Neurosurg

    (2003)
  • F. Maiuri

    The blood leukocyte count and its prognostic significance in subarachnoid hemorrhage

    J Neurosurg Sci

    (1987)
  • J. Oliveira-Filho

    Fever in subarachnoid hemorrhage: relationship to vasospasm and outcome

    Neurology

    (2001)
  • Cited by (15)

    • Biomarker discovery in cerebral vasospasm after aneurysmal subarachnoid hemorrhage

      2015, Journal of Stroke and Cerebrovascular Diseases
      Citation Excerpt :

      As stated previously, the breakdown of red blood cells and hemoglobin in subarachnoid space induces CV. Deoxyhemoglobin is the most prevalent irritant causing vasospasm whereas oxyhemoglobin is found to be elevated in patients with different forms of CV.14,43 Much like calcium, endothelial relaxing factors like nitric oxide–containing compounds affect vasoconstriction that occurs in vasospasm.14

    • Red Cell Distribution Width after Subarachnoid Hemorrhage

      2018, Journal of Neurosurgical Anesthesiology
    View all citing articles on Scopus
    View full text