Progressive metabolic and structural cerebral perturbations after traumatic brain injury: an in vivo imaging study in the rat.
Traumatic brain injury (TBI) has a high incidence of long-term neurologic and neuropsychiatric morbidity. Metabolic and structural changes in rat brains were assessed after TBI using serial (18)F-FDG PET and 3-dimensional MRI in vivo.


METHODS
Rats underwent lateral fluid percussion injury (FPI; n = 16) or a sham procedure (n = 11). PET and MR images were acquired at 1 wk and at 1, 3, and 6 mo after injury. Morphologic changes were assessed using MRI-based regions of interest, and hippocampal shape changes were assessed with large-deformation high-dimensional mapping. Metabolic changes were assessed using region-of-interest analysis and statistical parametric mapping with the flexible factorial analysis. Anxiety-like behavior and learning were assessed at 1, 3, and 6 mo after injury.


RESULTS
PET analyses showed widespread hypometabolism in injured rats, in particular involving the ipsilateral cortex, hippocampus, and amygdalae, present at 1 wk after FPI, most prominent at 1 mo, and then decreasing. Compared with the sham group, rats in the FPI group had decreased structural volume which progressively increased over 3-6 mo, occurring in the ipsilateral cortex, hippocampus, and ventricles after FPI (P < 0.05). Large-deformation high-dimensional mapping showed evolving hippocampal shape changes across the 6 mo after FPI. Injured rats displayed increased anxiety-like behavior (P < 0.05), but there were no direct correlations between the severity of the behavior abnormalities and functional or structural imaging changes.


CONCLUSIONS
In selected brain structures, FPI induces early hypometabolism and delayed progressive atrophic changes that are dynamic and continue to evolve for months. These findings have implications for the understanding of the pathophysiology and evolution of long-term neurologic morbidity following TBI, and indicate an extended window for targeted neuroprotective interventions.
Department of Medicine, The Royal Melbourne Hospital, University of Melbourne, Victoria, Australia.
Ying R
YR
Liu
Lisa
L
Cardamone
R Edward
RE
Hogan
Marie-Claude
MC
Gregoire
John P
JP
Williams
Rod J
RJ
Hicks
David
D
Binns
Amelia
A
Koe
Nigel C
NC
Jones
Damian E
DE
Myers
Terence J
TJ
O'Brien
Viviane
V
Bouilleret
D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D001930:Brain Injuries / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D019788:Fluorodeoxyglucose F18; D006624:Hippocampus / Q000473:pathology; D007858:Learning; D008279:Magnetic Resonance Imaging; D008297:Male; D010474:Percussion; D049268:Positron-Emission Tomography; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D019788:Fluorodeoxyglucose F18