Department of Neurological Surgery, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0112, USA.
J Neurotrauma. 2012 Nov 20;29(17):2672-83. doi: 10.1089/neu.2012.2595.
The pediatric brain may be particularly vulnerable to social deficits after traumatic brain injury (TBI) due to the protracted nature of psychosocial development through adolescence. However, the majority of pre-clinical studies fail to assess social outcomes in experimental pediatric TBI. The current study evaluated social behavior in mice subjected to TBI at post-natal day (p)21. Social behaviors were assessed by a partition test, resident-intruder, three-chamber, and tube dominance tasks during adolescence (p35-42) and again during early adulthood (p60-70), during encounters with unfamiliar, naïve stimulus mice. Despite normal olfactory function and normal social behaviors during adolescence, brain-injured mice showed impaired social investigation by adulthood, evidenced by reduced ano-genital sniffing and reduced following of stimulus mice in the resident-intruder task, as well as a loss of preference for sociability in the three-chamber task. TBI mice also lacked a preference for social novelty, suggestive of a deficit in social recognition or memory. By adulthood, brain-injured mice exerted more frequent dominance in the tube task compared to sham-operated controls, a finding suggestive of aggressive tendencies. Together these findings reveal reduced social interaction and a tendency towards increased aggression, which evolves across development to adulthood. This emergence of aberrant social behavior, which parallels the development of other cognitive deficits in this model and behaviors seen in brain-injured children, is consistent with the hypothesis that the full extent of deficits is not realized until the associated skills reach maturity. Thus, efficacy of therapeutics for pediatric TBI should take into account the time-dependent emergence of abnormal behavioral patterns.
由于青少年时期心理社会发展的长期性，小儿大脑可能特别容易受到创伤性脑损伤 (TBI) 后的社交缺陷的影响。然而，大多数临床前研究未能评估实验性小儿 TBI 的社交结果。本研究在出生后第 21 天（p21）评估了 TBI 后小鼠的社会行为。在青春期（p35-42）和成年早期（p60-70）期间，通过隔板测试、常驻入侵者、三室和管优势任务评估社交行为，在此期间与陌生、幼稚的刺激小鼠相遇。尽管嗅觉功能正常且青春期社会行为正常，但脑损伤小鼠在成年后表现出社交探究受损，表现为肛门生殖器嗅探减少，在常驻入侵者任务中跟随刺激小鼠减少，以及在三室任务中失去社交偏好。TBI 小鼠也缺乏对社交新颖性的偏好，这表明存在社交识别或记忆缺陷。成年后，与假手术对照组相比，脑损伤小鼠在管任务中更频繁地表现出优势，这一发现表明存在攻击性倾向。这些发现共同揭示了社交互动减少和攻击性增加的趋势，这种趋势随着发展而发展到成年。这种异常社交行为的出现与该模型中其他认知缺陷的发展以及脑损伤儿童的行为相吻合，这与这样一种假设一致，即只有当相关技能成熟时，缺陷的全部程度才会显现出来。因此，儿科 TBI 的治疗效果应该考虑到异常行为模式的时间依赖性出现。
