Division of Pediatric Rehabilitation Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Department of Biological Sciences, University of Cincinnati, Cincinnati, Ohio.
J Neurosci Res. 2020 Mar;98(3):557-570. doi: 10.1002/jnr.24535. Epub 2019 Sep 20.
Traumatic brain injury (TBI) is a major public health concern affecting 2.8 million people per year in the United States, of whom about 1 million are children under 19 years old. Animal models of TBI have been developed and used in multiple ages of animals, but direct comparisons of adult and adolescent populations are rare. The current studies were undertaken to directly compare outcomes between adult and adolescent male mice, using a closed head, single-impact model of TBI. Six-week-old adolescent and 9-week-old adult male mice were subjected to mild-moderate TBI. Histological measures for neurodegeneration, gliosis, and microglial neuroinflammation, and behavioral tests of locomotion and memory were performed. Adolescent TBI mice have increased mortality (Χ = 20.72, p < 0.001) compared to adults. There is also evidence of hippocampal neurodegeneration in adolescents that is not present in adults. Hippocampal neurodegeneration correlates with histologic activation of microglia, but not with increased astrogliosis. Adults and adolescents have similar locomotion deficits after TBI that recover by 16 days postinjury. Adolescents have memory deficits as evidenced by impaired novel object recognition between 3-4 and 4-16 days postinjury (F = 5.23, p = 0.031) while adults do not. In conclusion, adults and adolescents within a close age range (6-9 weeks) respond to TBI differently. Adolescents are more severely affected by mortality, neurodegeneration, and inflammation in the hippocampus compared to adults. Adolescents, but not adults, have worse memory performance after TBI that lasts at least 16 days postinjury.
创伤性脑损伤（TBI）是一个重大的公共卫生问题，每年影响美国 280 万人，其中约 100 万人是 19 岁以下的儿童。已经开发并使用了多种动物模型来研究 TBI，但将成年和青少年群体进行直接比较的情况很少。本研究旨在使用 TBI 的闭合性颅脑单次冲击模型，直接比较成年和青少年雄性小鼠之间的结果。将 6 周龄的青少年和 9 周龄的成年雄性小鼠进行轻度至中度 TBI。进行神经退行性变、神经胶质增生和小胶质细胞神经炎症的组织学测量，以及运动和记忆行为测试。与成年人相比，青少年 TBI 小鼠的死亡率更高（Χ ²= 20.72，p < 0.001）。青少年的海马神经退行性变证据也不存在于成年人中。海马神经退行性变与小胶质细胞的组织学激活相关，但与星形胶质细胞增生无关。TBI 后，成年人和青少年的运动缺陷相似，在损伤后 16 天恢复。青少年的记忆缺陷表现为损伤后 3-4 天至 4-16 天之间新物体识别受损（F = 5.23，p = 0.031），而成年人则没有。总之，在接近的年龄范围内（6-9 周），成年人和青少年对 TBI 的反应不同。与成年人相比，青少年的死亡率、海马神经退行性变和炎症更为严重。与成年人相比，青少年在 TBI 后至少 16 天的记忆表现更差。
