Altered levels of transthyretin in human cerebral microdialysate after subarachnoid haemorrhage using proteomics; a descriptive pilot study

Abstract

Abstract Background Subarachnoid haemorrhage (SAH) is one of the most severe forms of stroke in which delayed cerebral ischemia is one of the major complications. Neurointensive care aims at preventing and treating such complications and identification of biomarkers of early signs of ischemia might therefore be helpful. Methods We aimed at describing proteome profile in cerebral microdialysate in four patients with aneurysmal SAH using two dimensional gel electrophoresis in combination with mass spectrometry in search for new biomarkers for delayed cerebral ischemia and to investigate if there were temporal fluctuations in those biomarkers over time after aneurysmal bleed. Results The results showed transthyretin in nine different proteoforms (1001, 1102, 2101, 3101, 4101, 4102, 5001, 5101, 6101) in cerebral microdialysate samples from four patients having sustained SAH. Several proteoforms show highly differing levels and pooled analysis of all samples showed varying optical density related to time from aneurysmal bleed, indicating a temporal evolution. Conclusions Transthyretin proteoforms have not earlier been shown in cerebral microdialysate after SAH and we describe differing levels based on proteoform as well as time from subarachnoid bleed. Transthyretin is well known to be synthetized in choroid plexus, whilst intraparenchymal synthesis remains controversial. The results need to be confirmed in larger studies in order to further describe transthyretin.

Keywords

• Proteomics; subarachnoid hemorrhage; microdialysis; transthyretin; prealbumin; biomarkers; brain ischemia