Rowe Rachel K, Ziebell Jenna M, Harrison Jordan L, Law L Matthew, Adelson P David, Lifshitz Jonathan
Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, Ariz., USA.
Dev Neurosci. 2016;38(3):195-205. doi: 10.1159/000446773. Epub 2016 Jul 23.
Development and aging are influenced by external factors with the potential to impact health throughout the life span. Traumatic brain injury (TBI) can initiate and sustain a lifetime of physical and mental health symptoms. Over 1.7 million TBIs occur annually in the USA alone, with epidemiology suggesting a higher incidence for young age groups. Additionally, increasing life spans mean more years to age with TBI. While there is ongoing research of experimental pediatric and adult TBI, few studies to date have incorporated animal models of pediatric, adolescent, and adult TBI to understand the role of age at injury across the life span. Here, we explore repeated behavioral performance between rats exposed to diffuse TBI at five different ages. Our aim was to follow neurological morbidities across the rodent life span with respect to age at injury. A single cohort of male Sprague-Dawley rats (n = 69) was received at postnatal day (PND) 10. Subgroups of this cohort (n = 11-12/group) were subjected to a single moderate midline fluid percussion injury at age PND 17, PND 35, 2 months, 4 months, or 6 months. A control group of naïve rats (n = 12) was assembled from this cohort. The entire cohort was assessed for motor function by beam walk at 1.5, 3, 5, and 7 months of age. Anxiety-like behavior was assessed with the open field test at 8 months of age. Cognitive performance was assessed using the novel object location task at 8, 9, and 10 months of age. Depression-like behavior was assessed using the forced swim test at 10 months of age. Age at injury and time since injury differentially influenced motor, cognitive, and affective behavioral outcomes. Motor and cognitive deficits occurred in rats injured at earlier developmental time points, but not in rats injured in adulthood. In contrast, rats injured during adulthood showed increased anxiety-like behavior compared to uninjured control rats. A single diffuse TBI did not result in chronic depression-like behaviors or changes in body weight among any groups. The interplay of age at injury and aging with an injury are translationally important factors that influence behavioral performance as a quality of life metric. More complete understanding of these factors can direct rehabilitative efforts and personalized medicine for TBI survivors.
发育和衰老受外部因素影响，这些因素有可能在整个生命周期中影响健康。创伤性脑损伤（TBI）可引发并持续一生的身心健康症状。仅在美国，每年就发生超过170万例创伤性脑损伤，流行病学研究表明年轻年龄组的发病率更高。此外，寿命延长意味着创伤性脑损伤患者的衰老时间更长。虽然目前正在对儿童和成人创伤性脑损伤进行实验研究，但迄今为止，很少有研究纳入儿童、青少年和成人创伤性脑损伤的动物模型，以了解不同年龄阶段受伤所起的作用。在此，我们探讨了在五个不同年龄遭受弥漫性创伤性脑损伤的大鼠之间的重复行为表现。我们的目的是追踪啮齿动物生命周期中与受伤年龄相关的神经病理学变化。在出生后第10天接收了一组雄性Sprague-Dawley大鼠（n = 69）。该组的亚组（每组n = 11 - 12）在出生后第17天、第35天、2个月、4个月或6个月时接受单次中度中线液压冲击损伤。从该组中选取一组未受伤的对照大鼠（n = 12）。在1.5、3、5和7月龄时通过横梁行走评估整个组的运动功能。在8月龄时用旷场试验评估焦虑样行为。在8、9和10月龄时使用新物体定位任务评估认知表现。在10月龄时用强迫游泳试验评估抑郁样行为。受伤年龄和受伤后的时间对运动、认知和情感行为结果有不同影响。在发育早期受伤的大鼠出现运动和认知缺陷，但成年期受伤的大鼠未出现。相比之下，成年期受伤的大鼠与未受伤的对照大鼠相比，焦虑样行为增加。单次弥漫性创伤性脑损伤在任何组中均未导致慢性抑郁样行为或体重变化。受伤年龄与衰老以及损伤之间的相互作用是影响行为表现（作为生活质量指标）的重要转化因素。对这些因素更全面的了解可为创伤性脑损伤幸存者的康复努力和个性化医疗提供指导。
