To understand the dynamics of progressive brain damage after lateral fluid-percussion induced traumatic brain injury (TBI) in rat, which is the most widely used animal model of closed head TBI in humans, MRI follow-up of 11 months was performed. The evolution of tissue damage was quantified using MRI contrast parameters T2, T1ρ, diffusion (Dav), and tissue atrophy in the focal cortical lesion and adjacent areas: the perifocal and contralateral cortex, and the ipsilateral and contralateral hippocampus. In the primary cortical lesion area, which undergoes remarkable irreversible pathologic changes, MRI alterations start at 3 h post-injury and continue to progress for up to 6 months. In more mildly affected perifocal and hippocampal regions, the robust alterations in T2, T1ρ, and Dav at 3 h to 3 d post-injury normalize within the next 9-23 d, and thereafter, progressively increase for several weeks. The severity of damage in the perifocal and hippocampal areas 23 d post-injury appeared independent of the focal lesion volume. Magnetic resonance spectroscopy (MRS) performed at 5 and 10 months post-injury detected metabolic alterations in the ipsilateral hippocampus, suggesting ongoing neurodegeneration and inflammation. Our data show that TBI induced by lateral fluid-percussion injury triggers long-lasting alterations with region-dependent temporal profiles. Importantly, the temporal pattern in MRI parameters during the first 23 d post-injury can indicate the regions that will develop secondary damage. This information is valuable for targeting and timing interventions in studies aiming at alleviating or reversing the molecular and/or cellular cascades causing the delayed injury.
Bibliographical noteFunding Information:
This work was supported by the Academy of Finland, the Emil Aaltonen Foundation, the Sigrid Juselius Foundation, CURE (Citizens United for Research for Epilepsy), the Finnish Epilepsy Research Foundation, and the Finnish Cultural Foundation. We thank Mrs. Maarit Pulkkinen, Mr. Jarmo Hartikainen, Mrs. Merja Lukkari, and Jari Nissinen, Ph.D., for technical assistance, Nick Hayward, M.Sc., for revising the language of the manuscript, and Ivan Tkác providing the short echo time STEAM pulse sequence.