Metabolic and behavioral deficits following a routine surgical procedure in rats - PubMed (original) (raw)
Metabolic and behavioral deficits following a routine surgical procedure in rats
David B Frumberg et al. Brain Res. 2007.
Abstract
To test the hypothesis that functional metabolic deficits observed following surgical brain injury are associated with changes in cognitive performance in rodents, we performed serial imaging studies in parallel with behavioral measures in control animals and in animals with surgical implants. Memory function was assessed using the novel object recognition (NOR) test, administered 3 days prior to and 3, 7, 14 and 56 days after surgery. At each time point, general locomotion was also measured. Metabolic imaging with 18F-fluorodeoxyglucose ([18F]FDG) occurred 28 and 58 days after surgery. Animals with surgical implants performed significantly worse on tests of object recognition, while general locomotion was unaffected by the implant. There was a significant decrease in glucose uptake after surgery in most of the hemisphere ipsilateral to the implant relative to the contralateral hemisphere. At both time points, the most significant metabolic deficits occurred in the primary motor cortex (-25%; p<0.001), sensory cortex (-15%, p<0.001) and frontal cortex (-12%; p<0.001). Ipsilateral areas further from the site of insertion became progressively worse, including the sensory cortex, dorsal striatum and thalamus. These data was supported by a voxel-based analysis of the PET data, which revealed again a unilateral decrease in [18F]FDG uptake that extended throughout the ipsilateral cortex and persisted for the duration of the 58-day study. Probe implantation in the striatum results in a widespread and long-lasting decline in cortical glucose metabolism together with a persistent, injury-related deficit in the performance of a cognitive (object recognition) task in rats.
Figures
Figure 1. NOR performance for pre-and post-injury and control animals
Graphs depict percentage of total investigation time that animals investigated the familiar (dark grey) or the novel (light grey) object during each of the 5 minute test sessions. This percentage was calculated as the ‘time at novel/total investigation time’ and as ‘time at familiar/total investigation time’. Bars indicate standard error of the mean (SEM). Significant differences in the duration of investigation at each object were determined with a two-tailed Student’s t-test in which *p<0.05, **p<0.01 and ***p<0.001.
Figure 2. Serial FDG scans of animals with implants versus controls (mean images)
In (a), an MRI atlas is provided for anatomical detail. Control animals at the 28 day time point are shown in (b) while mean images from cannulated animals are shown at 28 days (c) and 58 days (c) after the surgery. Red shows regions with highest normalized uptake. Cross hairs indicate the target coordinates of the stereotaxic implant in Paxinos and Watson brain space, +2.5, +0.5, -6 mm x, y, z from the surface of the brain.
Figure 3. Glass–brain representation of the clusters with a significantly decreased [18F]FDG accumulation in the surgical implant group as compared with the control group at 28 days after cannulation
Clusters were delineated from the SPM{T} map by a height threshold of T > 3.16 and by the threshold of cluster size over 100 contiguous voxels with the contrast of the control group minus the surgically implanted group.
Figure 4. Changes in basal [18F]FDG uptake 58 days following microdialysis probe implant targeting the right striatum
Numbers below the slices indicate their position relative to bregma in millimeters according to a standard rat brain atlas. Depicted in (a) and (b) are coronal slices (anterior-posterior coordinates, AP), in (c) and (d), transverse slices (dorsal-ventral coordinates, DV) and in (e), a sagittal slices (2.5 mm lateral to bregma). Colored overlays show statistically significant positive (red) and negative (blue) differences of animals with surgical implants (n=6) compared to controls (n=7). Significance is shown with a t-statistic color scale corresponding to the level of significance at the voxel level.
References
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