Abstract

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 T 2, T 1ρ, diffusion ( D av), 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 T 2, T 1ρ, and D av 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.

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