Acute and late changes in N-acetyl-aspartate following diffuse axonal injury in rats: an MRI spectroscopy and microdialysis study.

N-acetyl-aspartate (NAA) measured by proton nuclear magnetic resonance spectroscopy (1H-NMR) has been used as a marker of neuronal injury in many cerebral pathologies. Therefore, we evaluate the roles of microdialysis vs. 1H-NMR as techniques to assess NAA (NAAd; NAA/Creatine ratio) in the living brain, and compare the results with whole brain NAA (NAAw), analyzed by HPLC after diffuse traumatic brain injury (TBI). Acute (4 h post-injury survival) and late (48 h survival) changes were studied in a sham-operated group (Sham, n = 4), and two injured groups (TBI/4 h, n = 8; TBI/48 h, n = 7). Baseline NAAd was 8.17 +/- 1 microM, and there was no significant difference between groups. There was only a small (twice of control), but transient increase in NAAd in the TBI/4 h group after trauma. Baseline NAA/Cr ratio was 1.35 +/- 0.2, which did not change significantly between baseline, 1, 2, 3, 4 and 48 h or between groups after TBI. Whole brain NAAw (baseline 8.5 +/- 0.5 mmol kg-1 wet weight) did not differ significantly between groups before and after TBI. Diffuse TBI did not produce long-term changes in NAA, assessed by three different methods. These results may indicate that NAA is not a sensitive marker of the severity of diffuse axonal damage. However, further studies are needed to evaluate whether confounding factors such as microdialysis probe, voxel position and non-regional tissue homogenization might have influenced our data.

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.

Comparison of NAA measures by MRS and HPLC.

This work investigates the accuracy of an in vivo estimation of absolute N-acetyl aspartate (NAA) concentrations by magnetic resonance spectroscopy (MRS) using cerebral water as an internal reference standard. Single-voxel, proton spectroscopy was carried out in two groups of rats (normal and diffuse head injury), using a PRESS sequence with TR = 3 s, TE = 135 ms. Fully relaxed water spectra and water-suppressed proton spectra were obtained from a 7 x 5 x 5 mm3 volume of tissue. MRI-based brain water content measurements were also performed. Following MRS, HPLC determinations of NAA were carried out. In the normal rats the MRS yielded 10.98 +/- 0.83 mmol/kg w.w. vs 10.76 +/- 0.76 for HPLC with a mean absolute difference of 0.8. In the injured rats the corresponding results were 9.41 +/- 1.78 (MRS) and 8.16 +/- 0.77 (HPLC) with a mean absolute difference of 1.66. The in vivo absolute method accurately documented the temporal NAA changes compared to the NAA/Cr approach.