Evaluation of CA1 damage using single-voxel H-1-MRS and un-biased stereology: Can non-invasive measures of N-acetyl-asparate following global ischemia be used as a reliable measure of neuronal damage?

Global brain ischemia provoked by transient occlusion of the carotid arteri es (2VO) in gerbils results in a severe loss of neurons in the hippocampal CA1 region. We measured the concentration of the neuron specific N-acetyl-a spartate, [NAA], in the gerbil dorsal hippocampus by proton MR spectroscopy (H-1-MRS) in situ, and HPLC, 4 days after global ischemia. The [NAA] was c orrelated with graded hippocampus damage scoring and stereologically determ ined neuronal density. A basal hippocampal [NAA] of 8.37+/-0.10 and 9.81+/- 0.44 mmol/l were found from HPLC and LH-MRS, respectively. HPLC measurement s of [NAA] obtained from hippocampus 4 days after 2VO showed a 20% reductio n in the [NAA] following 4 min of ischemia (P<0.001). H-1-MRS measurements on gerbils subjected to 4 or 8 min of ischemia showed a similar 24% decline in the [NAA] (P<0.05). Thus, there was correlation between the HPLC and H- 1-MRS determined NAA decline. There was also a significant correlation betw een H-1-MRS [NAA] and the corresponding reduction in CA1 neuronal density ( P<0.004). In summary our findings show that single voxel H-1-MRS can be use d as a supplement to histological evaluation of neuronal injury in studies after global brain ischemia. Accordingly, volume selective spectroscopy has a potential for assessment of neuroprotective therapeutic compounds/strate gies with respect to neuronal rescue for delayed ischemic brain damage. (C) 2001 Elsevier Science B.V. All rights reserved.