Extracellular N-acetyl-aspartate as a biochemical marker of the severity of neuronal damage following experimental acute traumatic brain injury.
We evaluated the acute changes in interstitial and whole brain N-acetyl-aspartate (NAA) measured by high-performance liquid chromatography in animal models of isolated traumatic brain injury (TBI) and TBI combined with secondary insult (hypotension-hypoxia [HH]). The Marmarou impact-acceleration model was used. Four groups were studied: (1) sham-operated control, (2) TBI alone (TBI 500 gm, 2 m), (3) TBI plus 30 min of hypoxia (PaO2, approximately 40 mm Hg) and hypotension (mean arterial blood pressure, approximately 40 mm Hg) (THH), and (4) HH alone. The baseline value for dialysate NAA (NAAd) in the rats was 8.17+/-1 microM. No significant difference between groups was found for this baseline value. The TBI group had a modest (100%) transient increase in NAAd after isolated TBI. The HH group had a transient (500%) increase in NAAd at 1 h, sustained for 2 h. In the THH group, there was a persistent increase in NAAd (800%) that peaked at 2.5 h. The whole brain NAA (NAAw) concentration in controls was 8.5+/-0.5 mmol/kg wet weight. There was no significant difference between TBI and controls; however, there was a significant decrease in NAAw in the THH and HH group compared to controls. Thus, in this animal model of TBI and TBI with secondary insult, we found that persistent, marked elevation in NAA is associated with TBI and secondary ischemic/hypoxic insult, but not with isolated TBI alone.
Al-Samsam
R H
RH
Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0631, USA.
Alessandri
B
B
Bullock
R
R
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007022:Hypotension / Q000378:metabolism / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate