Extracellular N-acetylaspartate depletion in traumatic brain injury.
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.
Belli
Antonio
A
Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, London, UK.
Sen
Jon
J
Petzold
Axel
A
Russo
Salvatore
S
Kitchen
Neil
N
Smith
Martin
M
Tavazzi
Barbara
B
Vagnozzi
Roberto
R
Signoretti
Stefano
S
Amorini
Angela Maria
AM
Bellia
Francesco
F
Lazzarino
Giuseppe
G
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
D001224:Aspartic Acid; C000179:N-acetylaspartate