Abstract
BackgroundCerebral microdialysis (CMD) is a minimally invasive technique for sampling the interstitial fluid in human brain tissue. CMD allows monitoring the metabolic state of tissue, as well as sampling macromolecules such as proteins and peptides. Recovery of proteins or peptides can be hampered by their adsorption to the CMD membrane as has been previously shown in-vitro, however, protein adsorption to CMD membranes has not been characterized following implantation in human brain tissue.MethodsIn this paper, we describe the pattern of proteins adsorbed to CMD membranes compared to that of the microdialysate and of cerebrospinal fluid (CSF). We retrieved CMD membranes from three surgically treated intracerebral hemorrhage (ICH) patients, and analyzed protein adsorption to the membranes using two-dimensional gel electrophoresis (2-DE) in combination with nano-liquid mass spectrometry. We compared the proteome profile of three compartments; the CMD membrane, the microdialysate and ventricular CSF collected at time of CMD removal.ResultsWe found unique protein patterns in the molecular weight range of 10–35 kDa for each of the three compartments.ConclusionThis study highlights the importance of analyzing the membranes in addition to the microdialysate when using CMD to sample proteins for biomarker investigation.
Highlights
Sampling, detecting and analyzing protein biomarkers associated with ongoing brain injury is of growing interest in clinical neuroscience research, both in the acute setting of e.g. traumatic brain injury or intracerebral hemorrhage (ICH) as well as in chronic neurodegenerative diseases
We aimed to determine if there was a difference in proteome profile of cerebrospinal fluid (CSF), cerebral microdialysate, and on Cerebral microdialysis (CMD) membranes following implantation by using two-dimensional gel electrophoresis (2-DE) to separate proteins followed by identification by liquid chromatography tandem mass spectrometry (LC-MS/MS)
Microdialysate samples from six catheters, five CMD membranes and three CSF samples were available for proteomic analysis from three ICH patients
Summary
Sampling, detecting and analyzing protein biomarkers associated with ongoing brain injury is of growing interest in clinical neuroscience research, both in the acute setting of e.g. traumatic brain injury or intracerebral hemorrhage (ICH) as well as in chronic neurodegenerative diseases. CSF has the advantage of being relatively easy to obtain but does not entirely reflect the interstitial fluid [1, 2] Another method for sample collection, which does sample the interstitial fluid, is minimally invasive monitoring of brain tissue by cerebral microdialysis (CMD) used since the 1990s for monitoring brain metabolism as part of multimodal monitoring in the neurocritical care setting [3,4,5]. Recovery of proteins or peptides can be hampered by their adsorption to the CMD membrane as has been previously shown in-vitro, protein adsorption to CMD membranes has not been characterized following implantation in human brain tissue
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