Abstract
Mild traumatic brain injuries (mTBI) are common during adolescence, and limited clinical evidence suggests that a younger age at first exposure to a mTBI may lead to worse long-term outcomes. In this study, we hypothesized that a mTBI during adolescence would predispose toward poorer neurobehavioral and neuropathological outcomes after a subsequent injury at adulthood. Mice received a mild weight drop injury (mTBI) at adolescence (postnatal day 35; P35) and/or at adulthood (P70). Mice were randomized to 6 groups: ‘sham’ (sham-surgery at P35 only); ‘P35’ (mTBI at P35 only); ‘P35 + sham’ (mTBI at P35 + sham at P70); ‘sham + P70’ (sham at P35 + mTBI at P70); ‘sham + sham’ (sham at both P35 and P70); or ‘P35 + P70’ (mTBI at both P35 and P70). Acute apnea and an extended righting reflex time confirmed a mTBI injury at P35 and/or P70. Cognitive, psychosocial, and sensorimotor function was assessed over 1-week post-injury. Injured groups performed similarly to sham controls across all tasks. Immunofluorescence staining at 1 week detected an increase in glial activation markers in Sham + P70 brains only. Strikingly, 63% of Sham + P70 mice exhibited a skull fracture at impact, compared to 13% of P35 + P70 mice. Micro computed tomography of parietal skull bones found that a mTBI at P35 resulted in increased bone volume and strength, which may account for the difference in fracture incidence. In summary, a single mTBI to the adolescent mouse brain did not exacerbate the cerebral effects of a subsequent mTBI in adulthood. However, the head impact at P35 induced significant changes in skull bone structure and integrity. These novel findings support future investigation into the consequences of mTBI on skull bone.
Highlights
Mild traumatic brain injuries during sports and recreational activities are a common injury in children and adolescents, with an estimated 1.1–1.9 million cases occurring annually in the US [1]
Based on the striking difference in skull fracture rate between these groups, whereby the P35 + P70 group had fewer fractures compared to Sham + P70 mice, we focused our attention on the parietal skull bone plate using μCT, comparing those that had an injury at P35 (P35 + sham) versus those that only received sham surgeries
Our study found that a single Mild traumatic brain injuries (mTBI) during adolescence did not exacerbate the short-term neurobehavioral or neuropathological consequences of a subsequent mTBI in adulthood
Summary
Mild traumatic brain injuries (mTBI) during sports and recreational activities are a common injury in children and adolescents, with an estimated 1.1–1.9 million cases occurring annually in the US [1]. Adolescents appear to have a high incidence of mTBI [2]. MTBI accounts for 5–13% of all sporting injuries [3,4,5]. In addition to a high incidence, Adolescent Plus Adult Concussion in Mice evidence suggests that the adolescent brain may be sensitive to the consequences of a mTBI compared to injuries sustained during childhood or adulthood [6,7,8,9]. A study of over 6,000 high school athletes found that those who suffered two or more mTBIs reported more physical and cognitive symptoms compared to those with only one mTBI [14]. Some intriguing studies have detected a degree of neuroprotection or preconditioning afforded by a prior head impact [22, 23]
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