1Department of Neurology,Soroka Medical Center,Ben-Gurion University of the Negev,Beer-Sheva,Israel.
2Division of Anesthesiology and Critical Care,Soroka Medical Center,Ben-Gurion University of the Negev,Beer-Sheva,Israel.
Can J Neurol Sci. 2018 Jul;45(4):451-461. doi: 10.1017/cjn.2017.302. Epub 2018 Jun 8.
Post-stroke depression (PSD) is the most frequent psychiatric complication following ischemic stroke. It affects up to 60% of all patients and is associated with increased morbidity and mortality following ischemic stroke. The pathophysiology of PSD remains elusive and appears to be multifactorial, rather than "purely" biological or psychosocial in origin. Thus, valid animal models of PSD would contribute to the study of the etiology (and treatment) of this disorder.
The present study depicts a rat model for PSD, using middle cerebral artery occlusion (MCAO). The two-way shuttle avoidance task, Porsolt forced-swim test, and sucrose preference test were employed to assess any depression-like behavior. Localized brain expressions of brain-derived neurotrophic factor (BDNF) protein levels were evaluated to examine the possible involvement of the brain neuronal plasticity in the observed behavioral syndrome. The raw data were subjected to unsupervised fuzzy clustering (UFC) algorithms to assess the sensitivity of bio-behavioral measures indicative of depressive symptoms post MCAO.
About 56% of the rats developed significant depressive-like behavioral disruptions as a result of MCAO compared with 4% in the sham-operated control rats. A pattern of a depressive-like behavioral response was common to all affected MCAO animals, characterized by significantly more escape failures and reduced number of total avoidance shuttles, a significant elevation in immobility duration, and reduced sucrose preference. Significant downregulations of BDNF protein levels in the hippocampal sub-regions, frontal cortex, and hypothalamus were observed in all affected MCAO animals.
The UFC analysis supports the behavioral analysis and thus, lends validity to our results.
中风后抑郁(PSD)是缺血性中风后最常见的精神并发症。它影响到所有患者的 60%以上,并且与缺血性中风后的发病率和死亡率增加有关。PSD 的病理生理学仍然难以捉摸,似乎是多因素的,而不是“纯粹”的生物学或心理社会起源。因此,有效的 PSD 动物模型将有助于研究这种疾病的病因(和治疗)。
本研究使用大脑中动脉闭塞(MCAO)描绘了 PSD 的大鼠模型。采用双向穿梭回避任务、Porsolt 强迫游泳试验和蔗糖偏好试验评估任何类似抑郁的行为。评估脑源性神经营养因子(BDNF)蛋白水平的局部脑表达,以检查观察到的行为综合征中脑神经元可塑性的可能参与。原始数据经过无监督模糊聚类(UFC)算法处理,以评估生物行为测量对 MCAO 后抑郁症状的敏感性。
与假手术对照组的 4%相比,约 56%的大鼠因 MCAO 而出现明显的类似抑郁的行为障碍。所有受影响的 MCAO 动物都表现出类似抑郁的行为反应模式,表现为逃避失败明显增加,总回避穿梭次数减少,不动时间显著延长,以及蔗糖偏好降低。所有受影响的 MCAO 动物的海马亚区、前额皮质和下丘脑的 BDNF 蛋白水平均显著下调。
UFC 分析支持行为分析,从而使我们的结果具有有效性。