Aging-Related Alterations of Glymphatic Transport in Rat: In vivo Magnetic Resonance Imaging and Kinetic Study.
Aging-Related Alterations of Glymphatic Transport in Rat: In vivo Magnetic Resonance Imaging and Kinetic Study.
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DOI：
10.3389/fnagi.2022.841798
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发表时间：
2022
影响因子：
4.8
通讯作者：
Jiang Q
中科院分区：
文献类型：
--
作者：
Li L;Ding G;Zhang L;Davoodi-Bojd E;Chopp M;Li Q;Zhang ZG;Jiang Q
脑衰老过程中受损的淋巴废物清除功能会导致代谢废物和神经毒性蛋白（如淀粉样蛋白-β、tau）的积累，从而导致神经系统疾病。然而，与年龄相关的淋巴功能障碍如何影响大脑不同区域并影响脑废物清除尚不清楚。我们利用动态对比增强磁共振成像（DCE-MRI）和先进的动力学模型研究了老龄大鼠脑中淋巴转运的变化。健康幼龄（3-4月龄）和成年（18-20月龄）雄性大鼠（n = 12/组）采用相同的MRI方案，包括t2加权成像和3D t1加权成像，并腹腔内注射造影剂（Gd-DTPA）。模型衍生的输注速率和清除率参数，表征脑脊液（CSF）示踪剂通过淋巴系统运输的动力学，在多个代表性脑区域进行了评估。利用对比诱导的时间信号曲线（TSCs）结合结构成像测量脑室内充满csf的变化。与年轻的大脑相比，在老年大脑中检测到淋巴运输功能的整体损伤，证明了整个大脑的输注和清除率都降低。在老年大脑中，脑室增大，脑脊液通过脑室区域的运输效率降低。虽然与年龄相关的淋巴功能障碍普遍存在，但我们的动力学量化表明，其影响在大脑区域之间存在很大差异，其中嗅球的影响最为严重，这表明淋巴功能的改变具有异质性和区域性的优先性。作为脑废物清除的主要外排途径之一，嗅球中淋巴活性的强烈抑制可能是与神经毒性物质积累相关的与年龄相关的神经退行性疾病的部分基础。我们的数据为大脑区域对大脑功能变化的脆弱性随年龄增长提供了新的见解。
Impaired glymphatic waste clearance function during brain aging leads to the accumulation of metabolic waste and neurotoxic proteins (e.g., amyloid-β, tau) which contribute to neurological disorders. However, how the age-related glymphatic dysfunction exerts its effects on different cerebral regions and affects brain waste clearance remain unclear. We investigated alterations of glymphatic transport in the aged rat brain using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and advanced kinetic modeling. Healthy young (3–4 months) and aged (18–20 months) male rats (n = 12/group) underwent the identical MRI protocol, including T2-weighted imaging and 3D T1-weighted imaging with intracisternal administration of contrast agent (Gd-DTPA). Model-derived parameters of infusion rate and clearance rate, characterizing the kinetics of cerebrospinal fluid (CSF) tracer transport via the glymphatic system, were evaluated in multiple representative brain regions. Changes in the CSF-filled cerebral ventricles were measured using contrast-induced time signal curves (TSCs) in conjunction with structural imaging. Compared to the young brain, an overall impairment of glymphatic transport function was detected in the aged brain, evidenced by the decrease in both infusion and clearance rates throughout the brain. Enlarged ventricles in parallel with reduced efficiency in CSF transport through the ventricular regions were present in the aged brain. While the age-related glymphatic dysfunction was widespread, our kinetic quantification demonstrated that its impact differed considerably among cerebral regions with the most severe effect found in olfactory bulb, indicating the heterogeneous and regional preferential alterations of glymphatic function. The robust suppression of glymphatic activity in the olfactory bulb, which serves as one of major efflux routes for brain waste clearance, may underlie, in part, age-related neurodegenerative diseases associated with neurotoxic substance accumulation. Our data provide new insight into the cerebral regional vulnerability to brain functional change with aging.
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影响因子：
4.2
作者：
Bullitt, Elizabeth;Zeng, Donglin;Mortamet, Benedicte;Ghosh, Arpita;Aylward, Stephen R.;Lin, Weili;Marks, Bonita L.;Smith, Keith
通讯作者：
Smith, Keith
影响因子：
4.2
作者：
Ding G;Chopp M;Li L;Zhang L;Davoodi-Bojd E;Li Q;Zhang Z;Jiang Q
通讯作者：
Jiang Q
影响因子：
5.3
作者：
Child, Kevin M.;Herrick, Daniel B.;Jang, Woochan
通讯作者：
Jang, Woochan
影响因子：
9.9
作者：
Devanand, D. P.;Lee, Seonjoo;Mayeux, Richard
通讯作者：
Mayeux, Richard
影响因子：
3.3
作者：
Harada CN;Natelson Love MC;Triebel KL
通讯作者：
Triebel KL