Influence of metabolic syndrome on cerebral perfusion and cognition.,Neurobiology of Disease

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Influence of metabolic syndrome on cerebral perfusion and cognition.
Neurobiology of Disease ( IF 5.1 ) Pub Date : 2020-01-21 , DOI: 10.1016/j.nbd.2020.104756
Jessica M Livingston ₁ , Matthew W McDonald ₂ , Therese Gagnon ₁ , Matthew S Jeffers ₂ , Mariana Gomez-Smith ₁ , Sabina Antonescu ₁ , Greg O Cron ₃ , Carlie Boisvert ₄ , Baptiste Lacoste ₅ , Dale Corbett ₆

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Vascular cognitive impairment (VCI) is associated with chronic cerebral hypoperfusion (CCH) and memory deficits, and often occurs concurrently with metabolic syndrome (MetS). Despite their common occurrence, it is unknown whether CCH and MetS act synergistically to exacerbate VCI-associated pathology. Here, using male Sprague-Dawley rats, we examined the effects of a clinically relevant model of adolescent-onset MetS and adult-onset CCH on neuro-vascular outcomes, combining a cafeteria diet with a 2-vessel occlusion (2VO) model. Using longitudinal imaging, histology, and behavioural assessments, we identified several features of MetS and CCH including reduced cerebral blood volume, white matter atrophy, alterations in hippocampal cell density, and memory impairment. Furthermore, we identified a number of significant associations, potentially predictive of MetS and pathophysiological outcomes. White matter volume was positively correlated to HDL cholesterol; hippocampal cell density was negatively correlated to fasted blood glucose; cerebral blood flow and volume was negatively predicted by the combination of 2VO surgery and increased fasted blood glucose. These results emphasize the importance of including comorbid conditions when modeling VCI, and they outline a highly translational preclinical model that could be used to investigate potential interventions to mitigate VCI-associated pathology and cognitive decline.

中文翻译：

代谢综合征对脑灌注和认知的影响。

血管性认知障碍（VCI）与慢性脑灌注不足（CCH）和记忆力减退有关，并经常与代谢综合征（MetS）同时发生。尽管它们共同发生，但尚不清楚CCH和MetS是否协同作用以加剧VCI相关的病理。在这里，我们使用雄性Sprague-Dawley大鼠，结合自助餐厅饮食与2血管闭塞（2VO）模型，研究了青少年期MetS和成人期CCH对临床相关模型对神经血管结局的影响。使用纵向成像，组织学和行为评估，我们确定了MetS和CCH的几个特征，包括脑血容量减少，白质萎缩，海马细胞密度改变和记忆障碍。此外，我们发现了许多重要的关联，可能预测MetS和病理生理结果。白质量与高密度脂蛋白胆固醇呈正相关。海马细胞密度与空腹血糖呈负相关。2VO手术和空腹血糖升高相结合，对脑血流量和血容量的预测为阴性。这些结果强调了在对VCI建模时包括合并症的重要性，并且它们概述了高度转化的临床前模型，可用于研究潜在的干预措施，以减轻与VCI相关的病理和认知能力下降。2VO手术和空腹血糖升高相结合，对脑血流量和血容量进行了负面预测。这些结果强调了在对VCI建模时包括合并症的重要性，并且它们概述了高度转化的临床前模型，可用于研究潜在的干预措施，以减轻与VCI相关的病理和认知能力下降。2VO手术和空腹血糖升高相结合，对脑血流量和血容量进行了负面预测。这些结果强调了在对VCI建模时包括合并症的重要性，并且它们概述了高度转化的临床前模型，可用于研究潜在的干预措施，以减轻与VCI相关的病理和认知能力下降。

更新日期：2020-01-22

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