Heart failure (HF) is associated with progressive reduction in cerebral blood flow (CBF) and neurodegenerative changes leading to cognitive decline. The glymphatic system is crucial for the brain's waste removal, and its dysfunction is linked to neurodegeneration. In this study, we used a mouse model of HF, induced by myocardial infarction (MI), to investigate the effects of HF with reduced ejection fraction on the brain’s glymphatic function. Using dynamic contrast-enhanced MRI and high-resolution fluorescence microscopy, we found increased solute influx from the CSF spaces to the brain, i.e. glymphatic influx, at 12 weeks post MI. Two-photon microscopy revealed that cerebral arterial pulsatility, a major driver of the glymphatic system, was potentiated at this timepoint, and could explain this increase in glymphatic influx. However, clearance of proteins from the brain parenchyma did not increase proportionately with influx, while a relative increase in brain parenchyma volume was found at 12 weeks post MI, suggesting dysregulation of brain fluid dynamics. Additionally, our results showed a correlation between brain clearance and CBF. These findings highlight the role of CBF as a key regulator of the glymphatic system, suggesting its involvement in the development of brain disorders associated with reduced CBF. This study paves the way for future investigations into the effects of cardiovascular diseases on the brain's clearance mechanisms, which may provide novel insights into the prevention and treatment of cognitive decline.

中文翻译：

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心力衰竭中淋巴稳态丧失


心力衰竭 （HF） 与脑血流量 （CBF） 的进行性减少和导致认知能力下降的神经退行性变化有关。淋巴系统对于大脑的废物清除至关重要，其功能障碍与神经退行性变有关。在这项研究中，我们使用了心肌梗死 （MI） 诱导的 HF 小鼠模型来研究射血分数降低的 HF 对大脑淋巴功能的影响。使用动态对比增强 MRI 和高分辨率荧光显微镜，我们发现在 MI 后 12 周，从 CSF 空间流向大脑的溶质流入增加，即淋巴流入。双光子显微镜显示，脑动脉搏动是淋巴系统的主要驱动因素，在这个时间点增强，可以解释淋巴流入的增加。然而，脑实质中蛋白质的清除率并未随流入成比例增加，而在 MI 后 12 周发现脑实质体积相对增加，表明脑液动力学失调。此外，我们的结果显示大脑清除率与 CBF 之间存在相关性。这些发现强调了 CBF 作为淋巴系统关键调节剂的作用，表明它参与了与 CBF 降低相关的脑部疾病的发展。这项研究为未来研究心血管疾病对大脑清除机制的影响铺平了道路，这可能为预防和治疗认知能力下降提供新的见解。