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Updated: Jun 6, 2026
A Volumetric Method for Quantification of Cerebral Vasospasm in a Murine Model of Subarachnoid Hemorrhage
Published on: July 28, 2018
Metallomics study in CSF for putative biomarkers to predict cerebral vasospasm
Yaofang Zhang1, Joseph F Clark, Gail Pyne-Geithman
1Department of Chemistry, University of Cincinnati, OH 45221-0172, USA.
Insights
Cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH) is poorly understood. Analyzing cerebrospinal fluid (CSF) identified potential protein biomarkers for predicting CV, offering hope for better patient outcomes.
Area of Science:
- Neuroscience
- Biochemistry
- Analytical Chemistry
Background:
- Cerebral vasospasm (CV) is a dangerous narrowing of brain arteries after subarachnoid hemorrhage (SAH), often leading to poor patient outcomes.
- A 3-7 day window exists between SAH and CV, offering a critical period for prediction and prevention.
- Current methods for predicting CV are inefficient, highlighting the need for improved diagnostic approaches.
Purpose of the Study:
- To investigate cerebrospinal fluid (CSF) components as potential indicators of SAH and the development of CV.
- To identify novel biomarkers in CSF for predicting and potentially preventing CV after SAH.
Main Methods:
- Analysis of CSF from healthy controls, SAH patients, and SAH patients with CV.
- Utilized two-dimensional separations coupled with elemental and molecular mass spectrometry.
- Employed size exclusion chromatography (SEC) with ICP-MS for metal species analysis.
- Applied RP-Chip/electrospray MS and database searching for metallopeptide and metalloprotein identification.
Main Results:
- Distinct molecular distribution patterns of metal species (Fe, Ni, Cu, Zn, Pb) were observed in CSF across the three groups.
- Identified potential metallopeptides and metalloproteins in tryptic digests of CSF.
- Discovered six protein families that may serve as candidate biomarkers for CV prediction.
Conclusions:
- Alterations in CSF components, particularly specific proteins and metal-binding species, correlate with SAH and CV.
- These identified protein families represent promising targets for developing effective biomarkers to predict and prevent CV.
- Further research into these CSF biomarkers could significantly improve management of SAH patients.
Abstract:
Cerebral vasospasm (CV) refers to physical narrowing of brain cerebral arteries due to over-contraction of the arterial wall, which often arises following a subarachnoid hemorrhage (SAH). CV is frequently associated with poorer outcomes in those patients. Between the ictus of SAH and its CV complication, there is a 3-7 days delay, which provides a time window to predict and possibly prevent the onset CV. Since the precise pathomechanism of CV is still unclear and approaches for predicting it are inefficient, more effective ways of predicting CV need to be developed. As a protective nourishing fluid flows through the subarachnoid space, cerebrospinal fluid (CSF) closely relates to the health states of the central nervous system (CNS). Analysis of CSF can provide invaluable information to diagnose, treat and prevent diseases of the CNS because of its relatively direct representation of events in the brain. Therefore, we assume that the components in CSF and their alterations may reflect the state of aneurismal SAH and the development of vasospasm. In this study, three types of CSF from healthy control, and patients who suffered SAH and its complication, CV, were investigated via two-dimensional separations in combination with elemental and molecular mass spectrometry detection for the identification of elemental species. Size exclusion chromatography (SEC) was initially used with selective metal detection by inductively coupled plasma mass spectrometry (ICPMS) for characterizing size distribution of metal species. Various molecular distribution patterns were exhibited at different metal detection points (Fe, Ni, Cu, Zn and Pb). Further identification of possible metallopeptides and metalloprotein in tryptic digested fractions from the three sample types were made via reverse phase (RP)-Chip and electrospray mass spectrometry (MS) in combination with the Spectrum Mill data base search engine accessing appropriate data bases. Comparisons were generated to show suggested protein similarities or differences across the three CSF sample types. Six protein families with possible protein markers were further identified, and may be considered as possible focus areas for discovering valuable biomarkers to preclude the debilitating or deadly vasospasm.
