Longitudinal MRI and MRSI characterization of the quinolinic acid rat model for excitotoxicity: peculiar apparent diffusion coefficients and recovery of N‐acetyl aspartate levels

Abstract

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.

A longitudinal study of magnetic resonance spectroscopy Huntington's disease biomarkers

“…Similar amelioration of NAA deficits was noted after creatine administration to R6/2 mice . Recovery of striatal NAA deficits after 3‐NP and QA injection occurs in rodents, in some cases coincident with partial motor or behavioral phenotype recovery, a finding unlikely to be explained solely by neurogenesis …”

Follow-up of cortical activity and structure after lesion with laser speckle imaging and magnetic resonance imaging in nonhuman primates

“…49 This observation would then be in line with the time course reported after ibotenic acid injection in the hippocampal formation, 48 as well as with excitotoxic lesion in rats. [49][50][51] It remains to be determined at which precise time point (between one and 3.5 weeks) the excitotoxic activity disappears, to turn into a cortical region with diminished cerebral blood flow, as compared to the pre-lesion reference level. However, as previously claimed based on ibotenic acid lesion in the hippocampus of monkeys, the edema associated to the lesion may, to a large extent, contribute to the hypersignal in the MRI imaging during a few weeks post-lesion.…”

Incense use and respiratory tract carcinomas

“…After 12 months, the NAA/Cho and NAA/Cr values had not fully returned to normal in our study. A relatively small population of irreversibly damaged neurons had probably undergone cell death (26). NAA synthesis was shut down and this may account for the decrease (26).…”

“…A relatively small population of irreversibly damaged neurons had probably undergone cell death (26). NAA synthesis was shut down and this may account for the decrease (26). NAA cannot be restored to normal levels because the neurons cannot regenerate (27).…”