Stroke causes severe and long-lasting symptoms in patients. Besides focal deficits such as speech impairment and limb weakness, stroke also results in neuropsychiatric symptoms, including fatigue, anxiety, and depression, which are debilitating and often impair post-stroke rehabilitation. However, in experimental stroke research, the study of neuropsychiatric symptoms and their therapeutic targeting has so far been largely neglected, which can be mainly attributed to the lack of appropriate tools to investigate such deficits in mice. Here, we report that neuropsychiatric symptoms can be differentiated from focal deficits and specifically modulated independent of treating the primary lesion. In order to achieve this, we developed a novel behavior analysis tool by assessing test performance of various tests, combining outcome parameters to cover functional domains of focal and neuropsychiatric symptoms, and finally weighted results into a time point-specific score. This weighted score enabled us to clearly differentiate focal deficits and neuropsychiatric symptoms and detect these until the chronic phase after stroke. Using this analysis tool, we detected that neutralizing systemic cytokines (TNF-α, IL-1β and IL-6) specifically ameliorated neuropsychiatric symptoms but did not affect focal deficits or lesion volume. Hence, most conventional studies analyzing only focal deficits and lesion volume as primary outcome measures would have missed these significant and translationally relevant therapeutic effects. We anticipate that these findings will encourage more detailed analyses of neuropsychiatric symptoms particularly for anti-inflammatory therapies in stroke and that the presented weighted composite score will facilitate this development.

中文翻译：

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通过优化的行为评估电池检测缺血性中风后细胞因子诱导的疾病行为

中风会导致患者出现严重而持久的症状。除了语言障碍和肢体无力等局灶性缺陷外，中风还会导致神经精神症状，包括疲劳、焦虑和抑郁，这些症状会使人虚弱，并经常损害中风后的康复。然而，在实验性中风研究中，迄今为止，神经精神症状及其治疗靶向的研究在很大程度上被忽视，这主要是由于缺乏适当的工具来研究小鼠的这种缺陷。在这里，我们报告说，神经精神症状可以与局灶性缺陷区分开来，并且可以独立于治疗原发病灶进行特异性调节。为了实现这一目标，我们通过评估各种测试的测试性能，开发了一种新颖的行为分析工具，结合结果参数以涵盖局灶性和神经精神症状的功能域，并最终将结果加权为特定时间点的分数。该加权评分使我们能够清楚地区分局灶性缺陷和神经精神症状，并在中风后的慢性期之前检测到这些症状。使用该分析工具，我们检测到中和全身细胞因子（TNF-α、IL-1β 和 IL-6）可特异性改善神经精神症状，但不影响局灶性缺陷或病变体积。因此，大多数仅将局灶性缺陷和病灶体积作为主要结果指标进行分析的传统研究会遗漏这些显着且与转化相关的治疗效果。