Abstract：
Although existing literature supports associations between cerebrovascular dysfunction and the emergence of depression and depressive symptoms, relatively little is known about underlying mechanistic pathways that may explain potential relationships. As such, an integrated understanding of these relationships in preclinical models could provide insight into the nature of the relationship, basic mechanistic linkages, and areas in which additional investment should be targeted. This scoping review was conducted in MEDLINE, EMBASE, and Scopus to outline the relationship between depressive symptoms and cerebrovascular dysfunction in preclinical animal models with an additional focus on the areas above. From 3,438 articles initially identified, 15 studies met the inclusion criteria and were included in the review. All studies reported a positive association between the severity of markers for cerebrovascular dysfunction and that for depressive symptoms in rodent models and this spanned all models for either pathology. Specific mechanistic links between the two such as chronic inflammation, elevated vascular oxidant stress, and altered serotonergic signaling were highlighted. Notably, almost all studies addressed outcomes in male animals, with a near complete lack of data from females, and there was little consistency in terms of how cerebrovascular dysfunction was assessed. Across nearly all studies was a lack of clarity for any \"cause and effect\" relationship between depressive symptoms and cerebrovascular dysfunction. At this time, it is reasonable to conclude that a correlative relationship clearly exists between the two, and future investigation will be required to parse out more specific aspects of this relationship.NEW & NOTEWORTHY This scoping review presents a structured evaluation of all relevant existing literature linking cerebral vasculopathy to depressive symptom emergence in preclinical models. Results support a definite connection between vascular dysfunction and depressive symptoms, highlighting the importance of chronic elevations in inflammation and oxidant stress, and impaired serotonergic signaling. The review also identified significant knowledge gaps addressing male versus female differences and limited clear mechanistic links between cerebral vasculopathy and depressive symptoms.
摘要：
虽然现有文献支持脑血管功能障碍与抑郁症和抑郁症状的出现之间的关联，对可能解释潜在关系的潜在机械途径知之甚少。因此，在临床前模型中对这些关系的综合理解可以提供对关系性质的洞察，基本的机械联系和应有针对性的额外投资领域。这次范围审查是在MEDLINE进行的，EMBASE和Scopus概述了临床前动物模型中抑郁症状与脑血管功能障碍之间的关系，并进一步关注上述领域。从最初确定的3438篇文章中，15项研究符合纳入标准，被纳入综述。所有研究都报告了啮齿动物模型中脑血管功能障碍标志物的严重程度与抑郁症状之间的正相关，并且该模型涵盖了两种病理的所有模型。两者之间的具体机制联系，如慢性炎症，血管氧化应激升高，和改变的血清素能信号被突出显示。值得注意的是,几乎所有研究都针对雄性动物的结果，几乎完全缺乏女性的数据，在如何评估脑血管功能障碍方面几乎没有一致性。在几乎所有研究中，抑郁症状和脑血管功能障碍之间的任何“因果关系”关系都缺乏明确性。此时,这是合理的结论，相关关系显然存在于两者之间，未来的调查将需要解析出更具体的方面，以这种关系。
