Biochemical analysis of the cerebrospinal fluid: evidence for catastrophic energy failure and oxidative damage preceding brain death in severe head injury: a case report Luciano Cristofori a , Barbara Tavazzi b , Roberta Gambin a , Roberto Vagnozzi c , Stefano Signoretti d , Angela M. Amorini e , Giovanna Fazzina e , Giuseppe Lazzarino e, * a Department of Neurosurgery, University Hospital of Verona, Italy b Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Italy c Department of Neurosciences, Chair of Neurosurgery, University of Rome bTor Vergata,Q Italy d Department of Neurosciences, Division of Neurosurgery, bSan CamilloQ Hospital, Rome, Italy e Department of Chemical Sciences, Laboratory of Biochemistry, University of Catania, Italy Received 24 June 2004; received in revised form 2 September 2004; accepted 20 September 2004 Abstract Objectives: To compare biochemical and clinical parameters in a case of fatal severe traumatic brain injury (TBI) with secondary insult. Design and methods: A TBI patient was catheterized for intracranial pressure (ICP) monitoring and cerebrospinal fluid (CSF) analysis of ascorbate, malondialdehyde, oxypurines, and nucleosides. Results: Oxidative brain damage preceded ATP catabolite increment in the CSF even with ICP below 20 mm Hg. Sustained oxidative stress caused irreversible energy state derangement followed by a refractory ICP rise. Massive oxypurine and nucleoside release was recorded 36 h before brain death. Conclusions: Molecular events, detected by biochemical CSF analysis and preceding modification of clinical parameters in severe TBI with secondary insult, are discussed. D 2004 The Canadian Society of Clinical Chemists. All rights reserved. Keywords: Cerebrospinal fluid; Energy metabolism; High-performance liquid chromatography; Oxidative stress; Traumatic brain injury Introduction Experimental traumatic brain injury (TBI) causes release of excitatory amino acids [1], changes to cell ionic permeability [2], early occurrence of ROS-mediated oxida- tive stress, and is followed by profound impairment of cerebral energy metabolism [3,4]. The amount of oxidative damage, energy imbalance, and the eventual metabolic recovery are closely related to trauma severity [5]. In humans, these occurrences have not yet been clearly established, requiring research into what molecular events correlate with clinical evolution and with TBI patient outcome. By assaying cerebrospinal fluid (CSF) samples, we demonstrated that severe TBI patients are subjected to oxidative stress and energy metabolism alterations already during the time interval between TBI and hospital admission [6]. Similar results were obtained recently in infants and children suffering from TBI [7,8]. In this case report of a severe TBI patient with secondary insult, we present the time-course changes of biochemical parameters representative of ATP catabolism (oxypurines and nucleosides) and of ROS-mediated tissue damage (ascorbate and malondialdehyde) in CSF samples. On the basis of the biochemical and clinical patient evolution, we 0009-9120/$ - see front matter D 2004 The Canadian Society of Clinical Chemists. All rights reserved. doi:10.1016/j.clinbiochem.2004.09.013 * Corresponding author. Department of Chemical Sciences, Laboratory of Biochemistry, University of Catania, Viale A. Doria 6, 95125 Catania, Italy. Fax: +39 095337036. E-mail address: lazzarig@mbox.unict.it (G. Lazzarino). Clinical Biochemistry 38 (2005) 97 – 100