title: Extracellular N-acetylaspartate depletion in traumatic brain injury.
abstract: N-Acetylaspartate (NAA) is almost exclusively localized in neurons in the adult brain and is present in high concentration in the CNS. It can be measured by proton magnetic resonance spectroscopy and is seen as a marker of neuronal damage and death. NMR spectroscopy and animal models have shown NAA depletion to occur in various types of chronic and acute brain injury. We investigated 19 patients with traumatic brain injury (TBI). Microdialysis was utilized to recover NAA, lactate, pyruvate, glycerol and glutamate, at 12-h intervals. These markers were correlated with survival and a 6-month Glasgow Outcome Score. Eleven patients died and eight survived. A linear mixed model analysis showed a significant effect of outcome and of the interaction between time of injury and outcome on NAA levels (p = 0.009 and p = 0.004, respectively). Overall, extracellular NAA was 34% lower in non-survivors. A significant non-recoverable fall was observed in this group from day 4 onwards, with a concomitant rise in lactate-pyruvate ratio and glycerol. These results suggest that mitochondrial dysfunction is a significant contributor to poor outcome following TBI and propose extracellular NAA as a potential marker for monitoring interventions aimed at preserving mitochondrial function.
authors.affiliation: Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Antonio
authors.initials: A
authors.lastname: Belli
authors.forename: Jon
authors.initials: J
authors.lastname: Sen
authors.forename: Axel
authors.initials: A
authors.lastname: Petzold
authors.forename: Salvatore
authors.initials: S
authors.lastname: Russo
authors.forename: Neil
authors.initials: N
authors.lastname: Kitchen
authors.forename: Martin
authors.initials: M
authors.lastname: Smith
authors.forename: Barbara
authors.initials: B
authors.lastname: Tavazzi
authors.forename: Roberto
authors.initials: R
authors.lastname: Vagnozzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Signoretti
authors.forename: Angela Maria
authors.initials: AM
authors.lastname: Amorini
authors.forename: Francesco
authors.initials: F
authors.lastname: Bellia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lazzarino
mesh_terms: D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001923:Brain Chemistry; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D017551:Microdialysis; D008875:Middle Aged; D011180:Postmortem Changes; D013997:Time Factors
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate