Juvenile concussion results in accelerated aging:A diffusion MRI investigation

Abstract

AbstractBackgroundJuvenile mild traumatic brain injury (jmTBI) has the potential to elicit cognitive, adaptive, and socio‐behavioral decrements. Unknown is how early life concussions can lead to enduring effects into late adulthood. Studying jmTBI progression from an early concussive event to long term deficits in adulthood is critical for outcome prediction and the development of appropriate treatments. We hypothesized that a single jmTBI leads to an altered brain maturation, thereby producing temporally evolving microstructural deficits that eventually lead to late‐in‐life cognitive and behavioral deficits.MethodsWe investigated the long‐term effects of jmTBI in C57Bl6 mice at postnatal day 17 and mapped the temporal evolution of alteration in long‐term behavior and cognitive outcomes. Diffusion‐tensor MRI (DTI) and structural MRI were examined at 7 temporal epochs from 1 to 18mo post‐concussion. Regional MRI tissue analysis was performed using the AMBC mouse atlas. Confirmatory immunohistochemistry was also undertaken.ResultsjmTBI led to increased glial fibrillary acidic protein (GFAP) and neurofilament‐light (NFL) in blood samples and impaired spatial learning and memory was evident at 18mo. Extensive DTI longitudinal analysis from 1 to 18mo post‐concussion revealed that jmTBI produced temporally dependent deficits that were concurrent with behavioral impairments. DTI findings were concentrated at earlier timepoints (1‐3 m) and were correlated 10 behavioral deficits at 18m.ConclusionWe demonstrate that a single juvenile concussion early in life leads to lasting behavioral impairments later in life and which are linked to early regional tissue deficits. Our work not only establishes that juvenile concussions are chronic in nature with the potential to produce long‐lasting effects but provides an unprecedented insight into how an early concussions may produce adverse effects later in life.