A preliminary study of metalloproteins in CSF by CapLC-ICPMS and NanoLC-CHIP/ITMS

Cerebrospinal fluid (CSF) has frequently been studied to explore the total metal concentrations in patients with neurodegenerative diseases. Some examples of neurologic diseases include but are not limited to intracerebral hemorrhage, intraventricular hemorrhage, traumatic brain injury, subarachnoid hemorrhage and hydrocephalus. In this study, however, a comprehensive approach was begun using metallomics methods. First, two molecular weight cutoff filters were used to separate CSF constituents by molecular weight. The remaining CSF was then separated with capillary liquid chromatography/normal bore liquid chromatography and analyzed with inductively coupled mass spectrometry (ICPMS). With this ICPMS screening, a possible iron associated protein was suggested by nanoliquid chromatography-CHIP/ion trap mass spectrometry (nanoLC-CHIP/ITMS) identification in conjunction with a Spectrum Mill database search. In this preliminary study, three different types of pooled CSF were partially characterized by their metal (Pb, Mg, Zn, Fe and Cu) containing species with suggestions for fuller studies. Chemical 'differences' in the CSF and metal constituents suggests some utility in this analysis for understanding some of the complications observed following subarachnoid hemorrhage.