Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL, United States; Graduate Program in Biomedical Sciences, Neuroscience Concentration, University of Florida, United States.
Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL, United States.
Behav Brain Res. 2023 Feb 2;437:114106. doi: 10.1016/j.bbr.2022.114106. Epub 2022 Sep 8.
Approximately 60-70 million people suffer from traumatic brain injury (TBI) each year. Animal models continue to be paramount in understanding mechanisms of cellular dysfunction and testing new treatments for TBI. Enhancing the translational potential of novel interventions therefore necessitates testing pre-clinical intervention strategies with clinically relevant cognitive assays. This study used a unilateral parietal lobe controlled cortical impact (CCI) model of TBI and tested rats on a touchscreen-based Paired Associates Learning (PAL) task, which is part of the Cambridge Neuropsychological Test Automated Battery. In humans, the PAL task has been used to assess cognitive deficits in the ability to form stimulus-location associations in a multitude of disease states, including TBI. Although the use of PAL in animal models could be important for understanding the clinical severity of cognitive impairment post-injury and throughout intervention, to date, the extent to which a rat model of TBI produces deficits in PAL task performance has not yet been reported. This study details the behavioral consequences of the CCI injury model with a Trial-by-Trial analysis of PAL performance that enables behavioral strategy use to be inferred. Following behavior, the extent of the injury was quantified with histology and staining for the presence of glial fibrillary acid protein and ionized calcium-binding adapter molecule 1. Rats that received unilateral CCI were impaired on the PAL task and showed more aberrant response-driven behavior. The magnitude of PAL impairment was also correlated with Iba1 staining in the thalamus. These observations suggest that PAL could be useful for pre-clinical assessments of novel interventions for treating TBI.
每年大约有 6000 万至 7000 万人患有创伤性脑损伤 (TBI)。动物模型在理解细胞功能障碍的机制和测试 TBI 的新治疗方法方面仍然至关重要。因此，为了提高新干预措施的转化潜力，需要使用具有临床相关性的认知测定法来测试临床前干预策略。本研究使用单侧顶叶皮质控制的皮质撞击 (CCI) TBI 模型，并在基于触摸屏的配对联想学习 (PAL) 任务上对大鼠进行测试，该任务是剑桥神经心理学测试自动化电池的一部分。在人类中，PAL 任务已被用于评估在多种疾病状态（包括 TBI）下形成刺激 - 位置关联的能力的认知缺陷。尽管在动物模型中使用 PAL 对于理解损伤后和整个干预过程中的认知损伤的临床严重程度可能很重要，但迄今为止，尚未报道 TBI 大鼠模型在 PAL 任务表现中产生缺陷的程度。本研究详细介绍了 CCI 损伤模型的行为后果，并通过 PAL 性能的逐次分析来推断行为策略的使用。行为后，用组织学和神经胶质纤维酸性蛋白和钙结合衔接蛋白 1 的存在染色来量化损伤的程度。接受单侧 CCI 的大鼠在 PAL 任务中受损，并表现出更多异常的反应驱动行为。PAL 损伤的程度也与丘脑中的 Iba1 染色相关。这些观察结果表明，PAL 可能有助于 TBI 新型干预措施的临床前评估。
