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  • Multiplexed protein profiling after aneurysmal subarachnoid hemorrhage: characterization of differential expression patterns in cerebral vasospasm

    Final Number:

    Brian Patrick Walcott MD; Anoop Patel MD; Christopher J. Stapleton MD; Matthew Koch MD; Adam MH Young; Christopher S. Ogilvy MD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2014 Annual Meeting

    Introduction: Cerebral vasospasm is major contributor to delayed morbidity following aneurysmal subarachnoid hemorrhage. Early detection of cerebral vasospasm is essential, as it allows for the administration of medical and intra-arterial therapies in an attempt to prevent tissue ischemia and stroke. Currently available methods of vasospasm detection are serial clinical examination, transcranial Doppler (TCD) sonographic studies, and radiographic studies; plasma biomarkers are not used in routine clinical practice.

    Methods: We sought to evaluate differential plasma protein levels across time in patients with aneurysmal subarachnoid hemorrhage to identify potential biomarkers and to better understand the pathogenesis of cerebral vasospasm. Nine female patients with aneurysmal subarachnoid hemorrhage underwent serial analysis of 239 different serum protein levels using quantitative, multiplexed immunoassays (DiscoveryMAP 250+ v2.0, Mryiad RBM, Austin, TX USA) on post-hemorrhage days 0 and 5. A repeated measures ANOVA with a Greenhouse-Geisser correction was used to determine differences in protein concentration between groups.

    Results: Protein concentration decreased significantly in patients who developed vasospasm versus those that did not for alpha-2-macroglobulin (F(1.00, 7.00) = 16.33, p =0.005), angiogenin (F(1.00, 7.00) = 7.65, p= 0.028), apolipoprotein A-IV (F(1.00, 7.00) = 6.308, p=0.040), granulocyte colony-stimulating factor (F(1.00, 7.00) = 9.08, p=0.020), macrophage-stimulating protein (F(1.00, 7.00) = 24.21, p=0.002), tetranectin (F(1.00, 7.00) = 5.46, P < 0.039), vascular endothelial growth factor receptor 3 (F(1.00, 7.00) = 6.94, p= 0.034), and significantly increased for vitronectin (F(1.00, 7.00 = 5.79, p=0.047).

    Conclusions: Serum protein profiles are altered following subarachnoid hemorrhage and differ between patients that recover from their hemorrhage and those that go on to develop vasospasm. Serum biomarkers have the potential to identify patients at risk for vasospasm development, as well as to aide in the diagnosis of vasospasm.

    Patient Care: This preliminary study identifies potential biomarkers in vasospasm following subarachnoid hemorrhage.

    Learning Objectives: By the conclusion of this session, participants should be be able to: 1) Identify the commonly used methods of vasospasm detection, 2) Describe the technique of multiplexed protein profiling, 3) Identify the potential role of biomarkers in vasospasm and need for further study.


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