Detection of cytokine-induced sickness behavior after ischemic stroke by an optimized behavioral assessment battery
Detection of cytokine-induced sickness behavior after ischemic stroke by an optimized behavioral assessment battery
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通过优化的行为评估组检测缺血性中风后细胞因子诱发的疾病行为
DOI：
10.1016/j.bbi.2020.11.016
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Liesz A
中科院分区：
文献类型：
--
作者：
Roth S;Yang J;Cramer JV;Malik R;Liesz A
中风会给患者带来严重而持久的症状。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，并常常损害中风后的康复。然而，在脑卒中实验研究中，神经精神症状及其治疗靶向的研究迄今在很大程度上被忽视，这主要归因于缺乏适当的工具来研究小鼠的这种缺陷。在这里，我们报道神经精神症状可以从局灶性缺陷和特异性调节独立于治疗原发病变区分开来。为了实现这一目标，我们开发了一种新的行为分析工具，通过评估各种测试的测试表现，结合结果参数来涵盖局灶性和神经精神症状的功能领域，并最终将结果加权为特定时间点的评分。这个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检测到这些症状。使用该分析工具，我们发现中和的全身细胞因子（TNF-α， IL-1β和IL-6）特异性地改善了神经精神症状，但不影响局灶性缺陷或病变体积。因此，大多数传统研究只分析局灶缺陷和病变体积作为主要结局指标，会错过这些重要的和翻译相关的治疗效果。我们预计这些发现将鼓励对神经精神症状进行更详细的分析，特别是对中风的抗炎治疗，并且提出的加权综合评分将促进这一发展。
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.
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影响因子：
17.1
作者：
Llovera, Gemma;Hofmann, Kerstin;Liesz, Arthur
通讯作者：
Liesz, Arthur
DOI：
10.1007/bf03160168
发表时间：
1993-05-01
期刊：
MOLECULAR AND CHEMICAL NEUROPATHOLOGY
影响因子：
--
作者：
COMPSTON, A
通讯作者：
COMPSTON, A
影响因子：
17.1
作者：
Roth, Stefan;Singh, Vikramjeet;Liesz, Arthur
通讯作者：
Liesz, Arthur
影响因子：
2.9
作者：
Naess H;Nyland H
通讯作者：
Nyland H
影响因子：
4.7
作者：
Llovera, Gemma;Liesz, Arthur
通讯作者：
Liesz, Arthur