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.
Bibliographical noteFunding Information:
Supported by National Institutes of Health grant DA15082 and performed under Brookhaven Science Associates contract No. DE-AC02-98CH10886 with the U.S. Department of Energy. We greatly appreciate the efforts of David Alexoff, Colleen Shea, Lisa Muench, Youwen Xu and Drs. Joanna Fowler, Stephen Dewey, Mike Schueller, Paul Vaska, Richard Ferrieri and David Schlyer, and technical assistance from James Anselmini, Steve Howell and Barry Laffler in the BNL Chemistry Department.
- Brain injury
- Functional neuroimaging
- Glucose metabolism
- Parametric mapping