Biomarkers and Vasospasm After Aneurysmal Subarachnoid Hemorrhage
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
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2015, Journal of Stroke and Cerebrovascular DiseasesCitation 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
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