Zhang Lin, Levenson Cathy W, Salazar Valentina Cea, McCarthy Deirdre M, Biederman Joseph, Zafonte Ross, Bhide Pradeep G
Center for Brain Repair, Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida, USA.
Pediatric Psychopharmacology, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Dev Neurosci. 2021;43(1):63-72. doi: 10.1159/000515198. Epub 2021 Apr 13.
Attention deficit hyperactivity disorder (ADHD) increases the risk for concussion or mild traumatic brain injury (mTBI). At the same time, recommendations for the management of ADHD include participation in sports and other organized physical activities, including those that carry an increased risk of mTBI. Very little work has been done to determine the extent to which untreated ADHD adversely impacts behavioral outcomes of repeated mild concussions. Here, we used a perinatal nicotine exposure (PNE) mouse model of ADHD combined with a closed-head, repetitive mTBI model. The PNE mouse model carries significant construct, face, and predictive validity as a preclinical model of ADHD. Two-month-old PNE and control mice were subjected to closed-head repetitive mTBI or sham procedure once daily for 5 days. Object-based attention, novel object recognition memory, spatial working memory, and depression-like behavior were analyzed 1 day and 2 weeks following repeated mTBI. Consistent with our previous reports, mice in the PNE group showed significant deficits in object-based attention and working memory prior to mTBI. These deficits persisted following the repeated mTBI. Repeated mTBI produced a transient attention deficit in the control group but did not exacerbate the attention deficit that is characteristic of the PNE group. Although neither PNE nor repetitive mTBI alone influenced immobility in the tail suspension test, when PNE mice were subjected to mTBI, there was a transient increase in this measurement suggesting a synergistic effect of ADHD and mTBI on depression-like behavior. Thus, our data using the PNE mouse model suggest that ADHD may be a risk factor for transient depression following repeated mTBI and that repeated mTBI may be a risk factor for transient attention deficit.
注意力缺陷多动障碍（ADHD）会增加脑震荡或轻度创伤性脑损伤（mTBI）的风险。与此同时，ADHD的管理建议包括参与体育活动和其他有组织的体育锻炼，其中包括那些mTBI风险增加的活动。在确定未经治疗的ADHD对反复轻度脑震荡行为结果的不利影响程度方面，所做的工作非常少。在这里，我们使用了ADHD的围产期尼古丁暴露（PNE）小鼠模型，并结合了闭合性头部重复性mTBI模型。PNE小鼠模型作为ADHD的临床前模型具有显著的结构效度、表面效度和预测效度。对2个月大的PNE小鼠和对照小鼠每天进行一次闭合性头部重复性mTBI或假手术，持续5天。在反复mTBI后的1天和2周分析基于物体的注意力、新物体识别记忆、空间工作记忆和抑郁样行为。与我们之前的报告一致，PNE组小鼠在mTBI之前在基于物体的注意力和工作记忆方面表现出显著缺陷。这些缺陷在反复mTBI后仍然存在。反复mTBI在对照组中产生了短暂的注意力缺陷，但没有加剧PNE组特有的注意力缺陷。虽然单独的PNE或重复性mTBI都没有影响悬尾试验中的不动时间，但当PNE小鼠接受mTBI时，这一测量值出现了短暂增加，表明ADHD和mTBI对抑郁样行为有协同作用。因此，我们使用PNE小鼠模型的数据表明，ADHD可能是反复mTBI后短暂抑郁的一个风险因素，而反复mTBI可能是短暂注意力缺陷的一个风险因素。
