Article
Early changes in cerebral microdialysate proteins in patients with aneurysmal subarachnoid hemorrhage (SAH)
Frühe Vasospasmusmarker im Proteom des zerebralen Mikrodialysats bei Patienten mit aneurysmatischer SAB
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Published: | May 4, 2005 |
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Outline
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Objective
Detecting symptomatic vasospasm in high-grade SAH-patients remains challenging. We investigated protein expression in the cerebral microdialysate in SAH-patients suffering from delayed ischemic neurological deficits (DIND) and patients remaining asymptomatic and correlated this data with the cerebral microdialysate-metabolites.
Methods
A microdialysate catheter (CMA70, membrane length 10 mm, cut-off 20 kDa) was inserted subcortically into the region most likely to be affected by vasospasm after aneurysm-clipping. In 7 patients DIND developed and 7 others remained asymptomatic (matched for sex, age, WFNS-grade and aneurysm location). We analyzed proteomic profiles of the microdialysateof these patients 24 hours and 5-6 days after surgery by two-dimensional gel electrophoresis. In the first dimension, proteins were separated according to their isoelectric point, in the second dimension according to their molecular weight. We compared protein expression profiles by hierarchical clustering (EMBL online tool EPCLUST). Glucose, lactate, pyruvate, glutamate and glycerol were analyzed hourly using a bedside device (CMA 600).
Results
We found an average of 57±22 protein spots in the individual gels, ranging from 37 to 149. Cluster analysis identified an increase in concentrations of glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and an unidentified protein cluster, as well as a decreased concentration of Heat-shock-protein 73 (HSP73) in the vasospasm group 1.5±0.4 days after SAH. In patients with DIND, medians [25th, 75th quartile] of glutamate (3.8μM [1.5μM, 18.2μM]), lactate (2.9mM [1.5mM, 3.9mM]), L/P-ratio (20.5 [17.9, 30.4]) und glycerol (133.0μM [58.8μM, 294.8μM]) were increased compared to the asymptomatic group.
Conclusions
Cerebral microdialysis indicates changes in the metabolic and proteomic profile early after SAH in patients developing DIND. This might provide a chance to find prognostic markers to identify patients at risk and an early application of targeted therapy.