McColl Thomas J, Brady Rhys D, Shultz Sandy R, Lovick Lauren, Webster Kyria M, Sun Mujun, McDonald Stuart J, O'Brien Terence J, Semple Bridgette D
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia.
Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC, Australia.
Front Neurol. 2018 May 25;9:372. doi: 10.3389/fneur.2018.00372. eCollection 2018.
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-surgery at P35 only); (mTBI at P35 only); + (mTBI at P35 + sham at P70); + (sham at P35 + mTBI at P70); + (sham at both P35 and P70); or + (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.
轻度创伤性脑损伤（mTBI）在青少年时期很常见，有限的临床证据表明，首次暴露于mTBI时年龄越小，长期预后可能越差。在本研究中，我们假设青少年时期的mTBI会使成年后再次受伤时出现更差的神经行为和神经病理学结果。小鼠在青少年期（出生后第35天；P35）和/或成年期（P70）接受轻度重物坠落损伤（mTBI）。小鼠被随机分为6组：（仅在P35进行假手术）；（仅在P35进行mTBI）；+（P35进行mTBI + P70进行假手术）；+（P35进行假手术 + P70进行mTBI）；+（P35和P70均进行假手术）；或 +（P35和P70均进行mTBI）。急性呼吸暂停和延长的翻正反射时间证实了在P35和/或P70时的mTBI损伤。在损伤后1周内评估认知、心理社会和感觉运动功能。在所有任务中，受伤组的表现与假手术对照组相似。仅在Sham + P70组的大脑中，1周时的免疫荧光染色检测到胶质细胞激活标志物增加。令人惊讶的是，63%的Sham + P70小鼠在撞击时出现颅骨骨折，而P35 + P70小鼠的这一比例为13%。对顶骨颅骨的微型计算机断层扫描发现，P35时的mTBI导致骨体积和强度增加，这可能解释了骨折发生率上的差异。总之，对青春期小鼠大脑进行单次mTBI不会加重成年后再次mTBI的脑效应。然而，P35时的头部撞击引起了颅骨结构和完整性的显著变化。这些新发现支持未来对mTBI对颅骨影响的研究。
