Hippocampal demyelination is associated with increased magnetic susceptibility in a mouse model of concussion

Structural and functional deficits in the hippocampus are a prominent feature of moderate-severe traumatic brain injury (TBI). In this work, we investigated the potential of Quantitative Susceptibility Imaging (QSM) to reveal the temporal changes in myelin integrity in a mouse model of concussion (mild TBI). We employed a cross-sectional design wherein we assigned 43 mice to cohorts undergoing either a concussive impact or a sham procedure, with QSM imaging at day 2, 7, or 14 post-injury, followed by Luxol Fast Blue (LFB) myelin staining to assess the structural integrity of hippocampal white matter (WM). We assessed spatial learning in the mice using the Active Place Avoidance Test (APA), recording their ability to use visual cues to locate and avoid zone-dependent mild electrical shocks. QSM and LFB staining indicated changes in the stratum lacunosum-molecular layer of the hippocampus in the concussion groups, suggesting impairment of this key relay between the entorhinal cortex and the CA1 regions. These imaging and histology findings were consistent with demyelination, namely increased magnetic susceptibility to MR imaging and decreased LFB staining. In the APA test, sham animals showed fewer entries into the shock zone compared to the concussed cohort. Thus, we present radiological, histological, and behavioral findings that concussion can induce significant and alterations in hippocampal integrity and function that evolve over time after the injury.