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Longitudinal MRI and MRSI characterization of the quinolinic acid rat model for excitotoxicity: peculiar apparent diffusion coefficients and recovery of N‐acetyl aspartate levels
Author(s) -
Shemesh Noam,
Sadan Ofer,
Melamed Eldad,
Offen Daniel,
Cohen Yoram
Publication year - 2010
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1443
Subject(s) - quinolinic acid , excitotoxicity , striatum , lesion , in vivo , effective diffusion coefficient , chemistry , metabolite , nuclear medicine , stain , perfusion , pathology , neuroscience , magnetic resonance imaging , medicine , glutamate receptor , biology , biochemistry , staining , radiology , dopamine , amino acid , tryptophan , receptor , microbiology and biotechnology
Quinolinic acid (QA) induced striatal lesion is an important model for excitotoxicity that is also used for efficacy studies. To date, the morphological and spectroscopic indices of this model have not been studied longitudinally by MRI; therefore the objectives of this study were aimed at following the lesion progression and changes in N‐acetyl aspartate (NAA) as viewed by MRI and MRSI, respectively, in‐vivo over a period of 49 days. We found that the affected areas exhibited both high and low apparent diffusion coefficients (ADC) even 49 days post QA injection in three of the six tested animals. MRI‐guided histological analysis correlated areas characterized by high ADCs on day 49 with cellular loss, while areas characterized by lower ADCs were correlated with macrophage infiltration (CD68 positive stain). Our MRSI study revealed an initial reduction of NAA levels in the lesioned striatum, which significantly recovered with time, although not to control levels. Total‐striatum normalized NAA levels recovered from 0.67 ± 0.15 (of the contralateral row) on day 1 to 0.90 ± 0.12 on day 49. Our findings suggest that NAA should be considered as a marker for neuronal dysfunction, in addition to neuronal viability. Some behavioral indices could be correlated to permanent neuronal damage while others demonstrated a spontaneous recovery parallel to the NAA recovery. Our findings may have implications in efficacy‐oriented studies performed on the QA model. Copyright © 2009 John Wiley & Sons, Ltd.