4.6 Article

Aneurysmal Subarachnoid Hemorrhage Onset Alters Pyruvate Metabolism in Poor-Grade Patients and Clinical Outcome Depends on More: A Cerebrospinal Fluid Metabolomic Study

Journal

ACS CHEMICAL NEUROSCIENCE
Volume 10, Issue 3, Pages 1660-1667

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.8b00581

Keywords

Aneurysmal subarachnoid hemorrhage; metabolomics; cerebrospinal fluid; pyruvate metabolism; amino acid metabolism; lipid biosynthesis

Funding

  1. Nanjing Medical Science and Technique Development Foundation and Key Project [YKK10065, YKK13077]
  2. Medical Science and Technology Development Foundation, Nanjing Department of Health

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Cerebral metabolism alterations influence cerebrospinal fluid (CSF) composition and are sensitive to brain injury. In subarachnoid hemorrhage (SAH) patients, Fisher scale, Hunt Hess scale, and World Federation of Neurological Societies (WFNS) grading scale evaluating SAH severity are inadequate to predict long-term outcome; therefore, in an effort to determine metabolite pattern disparity and discover corresponding biomarkers, we designed an untargeted CSF metabolomic study covering a broad range of metabolites of SAH patients with different severity and outcome. The present study demonstrated the SAH altered the cerebrospinal fluid metabolome involving carbohydrate, lipid, and amino acid metabolism. Pyruvate metabolism was enhanced in SAH patients with Hunt Hess scale above III, and the CSF pyruvate level was significantly associated with WFNS grading scale above III. There is no significant variation among CSF metabolome in SAH patients with merely different amounts and distribution of bleeding. SAH patients with unfavorable outcome present upregulated CSF amino acids level and enhanced lipid biosynthesis. The present study provides a novel possibility of early identification of patients who might possess unfavorable outcome and further clarification of the underlying pathophysiology.

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