ArticlebioRxiv : the preprint server for biology2023
Progressive lifespan modifications in the corpus callosum following a single juvenile concussion in male mice monitored by diffusion MRI.
Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors at 3 institutions in 2 countries.
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Abstract
Introduction: The sensitivity of white matter (WM) in acute and chronic moderate-severe traumatic brain injury (TBI) has been established. In concussion syndromes, particularly in preclinical rodent models, there is lacking a comprehensive longitudinal study spanning the lifespan of the mouse. We previously reported early modifications to WM using clinically relevant neuroimaging and histological measures in a model of juvenile concussion at one month post injury (mpi) who then exhibited cognitive deficits at 12mpi. For the first time, we assess corpus callosum (CC) integrity across the lifespan after a single juvenile concussion utilizing diffusion MRI (dMRI). Methods: C57Bl/6 mice were exposed to sham or two severities of closed-head concussion (Grade 1, G1, speed 2 m/sec, depth 1mm; Grade 2, G2, 3m/sec, 3mm) using an electromagnetic impactor at postnatal day 17. Results: Whole CC analysis revealed altered FA and RD trajectories following juvenile concussion. Shams exhibited a temporally linear increase in FA with age while G1/G2 mice had plateaued FA values. G2 concussed mice exhibited high variance of dMRI metrics at 12mpi, which was attributed to the heterogeneity of TBI on the anterior CC. Regional analysis of dMRI metrics at the impact site unveiled significant differences between G2 and sham mice. The dMRI findings appear to be driven, in part, by loss of astrocyte process lengths and increased circularity and decreased cell span ratios in microglia. Conclusion: For the first time, we demonstrate progressive perturbations to WM of male mice after a single juvenile concussion across the mouse lifespan. The CC alterations were dependent on concussion severity with elevated sensitivity in the anterior CC that was related to astrocyte and microglial morphology. Our findings suggest that long-term monitoring of children with juvenile concussive episodes using dMRI is warranted, focusing on vulnerable WM tracts.
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