title: Longitudinal Metabolite Profiling of Cerebrospinal Fluid in Normal Pressure Hydrocephalus Links Brain Metabolism with Exercise-Induced VEGF Production and Clinical Outcome.
abstract: Idiopathic normal pressure hydrocephalus is a neurological disease caused by abnormal cerebrospinal fluid flow and presents with symptoms such as dementia. Current therapy involves the removal of excess cerebrospinal fluid by shunting. Not all patients respond to this therapy and biomarkers are needed that could facilitate the characterization of patients likely to benefit from this treatment. Here, we measure brain metabolism in normal pressure hydrocephalus patients by performing a novel longitudinal metabolomic profiling study of cerebrospinal fluid. We find that the levels of brain metabolites correlate with clinical parameters, the amount of vascular endothelial growth factor in the cerebrospinal fluid, and environmental stimuli such as exercise. Metabolomic analysis of normal pressure hydrocephalus patients provides insight into changes in brain metabolism that accompany cerebrospinal fluid disorders and may facilitate the development of new biomarkers for this condition.
authors.affiliation: Departments of Chemistry and Biology, University of Akron, Akron, OH, 44325, USA.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Neurological Surgery, Section of Pediatric and Congenital Neurological Surgery, CSF Physiology Laboratory, Neurological Institute Cleveland Clinic, Cleveland, OH, 44106, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neurological Surgery, Section of Pediatric and Congenital Neurological Surgery, CSF Physiology Laboratory, Neurological Institute Cleveland Clinic, Cleveland, OH, 44106, USA. markluciano@jhu.edu.|Department of Neurology and Neurosurgery, Johns Hopkins, Baltimore, MD, 21287, USA. markluciano@jhu.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Luciano
authors.affiliation: Departments of Chemistry and Biology, University of Akron, Akron, OH, 44325, USA. lshriver@uakron.edu.
authors.forename: Leah P
authors.initials: LP
authors.lastname: Shriver
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D055432:Metabolomics / Q000379:methods* / Q000639:trends; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Cerebrospinal fluid; Exercise; Global metabolomics; Normal pressure hydrocephalus; Vascular endothelial growth factor