Repeat Mild Traumatic Brain Injury in Adolescent Rats Increases Subsequent β-Amyloid Pathogenesis

Single moderate-to-severe traumatic brain injuries (TBIs) may increase subsequent risk for neurodegenerative disease by facilitating beta-amyloid (A beta) deposition. However, the chronic effects on A beta pathogenesis of repetitive mild TBIs (rTBI), which are common in adolescents and young adults, remain uncertain. We examined the effects of rTBI sustained during adolescence on subsequent deposition of A beta pathology in a transgenic APP/PS1 rat model. Transgenic rats received sham or four individual mild TBIs (rTBIs) separated by either 24- or 72-h intervals at post-natal day 35 (before A beta plaque deposition). Animals were euthanized at 12 months of age and underwent immunohistochemical analyses of A beta plaque deposition. Significantly greater hippocampal A beta plaque deposition was observed after rTBI separated by 24h relative to rTBI separated by 72h or sham injuries. These increases in hippocampal A beta plaque load were driven by increases in both plaque number and size. Similar, though less-pronounced, effects were observed in extrahippocampal regions. Increases in A beta plaque deposition were observed both ipsilaterally and contralaterally to the injury site and in both males and females. rTBIs sustained in adolescence can increase subsequent deposition of A beta pathology, and these effects are critically dependent on interinjury interval.