Cerebrospinal Fluid Metabolomics After Natural Product Treatment in an Experimental Model of Cerebral Ischemia

Abstract

Cerebrospinal fluid (CSF) is an important biofluid for diagnosis of and research on neurological diseases. However, in-depth metabolomic profiling of CSF remains an analytical challenge due to the small volume of samples, particularly in small animal models. In this work, we report the application of a high-performance chemical isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS) workflow for CSF metabolomics in Gastrodia elata and Uncaria rhynchophylla water extract (GUW)-treated experimental cerebral ischemia model of rat. The GUW is a commonly used Traditional Chinese Medicine (TCM) for hypertension and brain disease. This study investigated the amine- and phenol-containing biomarkers in the CSF metabolome. After GUW treatment for 7 days, the neurological deficit score was significantly improved with infarct volume reduction, while the integrity of brain histological structure was preserved. Over 1957 metabolites were quantified in CSF by dansylation LC-MS. The analysis of this comprehensive list of metabolites suggests that metabolites associated with oxidative stress, inflammatory response, and excitotoxicity change during GUW-induced alleviation of ischemic injury. This work is significant in that (1) it shows CIL LC-MS can be used for in-depth profiling of the CSF metabolome in experimental ischemic stroke and (2) identifies several potential molecular targets (that might mediate the central nervous system) and associate with pharmacodynamic effects of some frequently used TCMs.

Impact of Oxygen Concentration on Metabolic Profile of Human Placenta-Derived Mesenchymal Stem Cells As Determined by Chemical Isotope Labeling LC–MS

“…For instance, differential 12 C-/ 13 C-dansylation labeling LC–MS has been shown to be a powerful method for analyzing amine- and phenol-containing metabolites or the amine/phenol submetabolome . Dansylation LC–MS has been applied to analyze many different types of biological samples, such as cells, plasma, cerebrospinal fluid, and fecal matter, with relatively high submetabolome coverage (i.e., thousands of metabolites). − …”

Targeted metabolomics reveals serum changes of amino acids in mild to moderate ischemic stroke and stroke mimics

“…In addition, consistent with the previous studies (28,29), we also found that glutamine, phenylalanine and tyrosine levels were increased significantly in MB patients (Table 3). Gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, derived from glutamate was also observed to be enhanced and its increase could be explained as a potential protective change in response to the excitatory neurotoxicity (30). Interestingly, we found that glutamate levels in IS patients were not altered compared to control in the current study, which was in 10.3389/fneur.2023.1153193…”

Cerebrospinal Fluid Biomarkers for Diagnosis and the Prognostication of Acute Ischemic Stroke: A Systematic Review

“…One study [ 37 ] evaluated a macaque model of CSF. The remaining four studies [ 38 , 39 , 40 , 41 ] evaluated a rat model of ischemic stroke. All rat model studies evaluated the progression of ischemic stroke, which was defined as worsening of neurological symptoms in the early course of stroke presentation [ 42 ].…”