Longitudinal MRI and MRSI characterization of the quinolinic acid rat model for excitotoxicity: peculiar apparent diffusion coefficients and recovery of N-acetyl aspartate levels.
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.
Shemesh
Noam
N
School of Chemistry, The Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Israel.
Sadan
Ofer
O
Melamed
Eldad
E
Offen
Daniel
D
Cohen
Yoram
Y
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D001224:Aspartic Acid; C000179:N-acetylaspartate; D017378:Quinolinic Acid