Divergent brain solute clearance in rat models of cerebral amyloid angiopathy and Alzheimer’s disease
Summary: Brain waste clearance from the interstitial fluid environment is challenging to measure, which has contributed to controversy regarding the significance of glymphatic transport impairment for neurodegenerative processes. Dynamic contrast enhanced MRI (DCE-MRI) with cerebrospinal fluid admin...
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Elsevier
2024-12-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224026907 |
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| author | Sunil Koundal Xinan Chen Zachary Gursky Hedok Lee Kaiming Xu Feng Liang Zhongcong Xie Feng Xu Hung-Mo Lin William E. Van Nostrand Xianfeng Gu Rena Elkin Allen Tannenbaum Helene Benveniste |
| author_facet | Sunil Koundal Xinan Chen Zachary Gursky Hedok Lee Kaiming Xu Feng Liang Zhongcong Xie Feng Xu Hung-Mo Lin William E. Van Nostrand Xianfeng Gu Rena Elkin Allen Tannenbaum Helene Benveniste |
| author_sort | Sunil Koundal |
| collection | DOAJ |
| description | Summary: Brain waste clearance from the interstitial fluid environment is challenging to measure, which has contributed to controversy regarding the significance of glymphatic transport impairment for neurodegenerative processes. Dynamic contrast enhanced MRI (DCE-MRI) with cerebrospinal fluid administration of Gd-tagged tracers is often used to assess glymphatic system function. We previously quantified glymphatic transport from DCE-MRI data utilizing regularized optimal mass transport (rOMT) analysis, however, information specific to glymphatic clearance was not directly derived. To fill this knowledge gap, we here implemented unbalanced rOMT analysis which allows for assessment of both influx and clearance. Dynamic influx/clearance brain maps were derived from rTg-DI rats with cerebral amyloid angiopathy (CAA) and TgSD-AD rats with Alzheimer’s disease (AD). The rTg-DI rats with severe CAA disease exhibited abnormal influx/clearance kinetics, while TgSD-AD rats with a moderate Aβ plaque load exhibited normal transport suggesting that different Aβ lesions and their overall burden differentially impact glymphatic system function. |
| format | Article |
| id | doaj-art-4feca50205da422f86d5f2fe7ab9b078 |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-4feca50205da422f86d5f2fe7ab9b0782025-08-20T02:35:04ZengElsevieriScience2589-00422024-12-01271211146310.1016/j.isci.2024.111463Divergent brain solute clearance in rat models of cerebral amyloid angiopathy and Alzheimer’s diseaseSunil Koundal0Xinan Chen1Zachary Gursky2Hedok Lee3Kaiming Xu4Feng Liang5Zhongcong Xie6Feng Xu7Hung-Mo Lin8William E. Van Nostrand9Xianfeng Gu10Rena Elkin11Allen Tannenbaum12Helene Benveniste13Department of Anesthesiology, Yale School of Medicine, New Haven, CT 06510, USADepartment of Medical Physics, Memorial Sloan Kettering Cancer Center, New York City, NY 10065, USADepartment of Anesthesiology, Yale School of Medicine, New Haven, CT 06510, USADepartment of Anesthesiology, Yale School of Medicine, New Haven, CT 06510, USADepartment of Anesthesiology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Applied Mathematics & Statistics, Stony Brook University, Stony Brook, NY 11794, USADepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USADepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USAGeorge and Anne Ryan Institute for Neuroscience and the Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02906, USADepartment of Anesthesiology, Yale School of Medicine, New Haven, CT 06510, USAGeorge and Anne Ryan Institute for Neuroscience and the Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02906, USADepartment of Applied Mathematics & Statistics, Stony Brook University, Stony Brook, NY 11794, USA; Departments of Computer Science, Stony Brook University, Stony Brook, NY 11794, USADepartment of Medical Physics, Memorial Sloan Kettering Cancer Center, New York City, NY 10065, USADepartment of Applied Mathematics & Statistics, Stony Brook University, Stony Brook, NY 11794, USA; Departments of Computer Science, Stony Brook University, Stony Brook, NY 11794, USADepartment of Anesthesiology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Biomedical Engineering, Yale School of Medicine New Haven, New Haven, CT 06510, USA; Corresponding authorSummary: Brain waste clearance from the interstitial fluid environment is challenging to measure, which has contributed to controversy regarding the significance of glymphatic transport impairment for neurodegenerative processes. Dynamic contrast enhanced MRI (DCE-MRI) with cerebrospinal fluid administration of Gd-tagged tracers is often used to assess glymphatic system function. We previously quantified glymphatic transport from DCE-MRI data utilizing regularized optimal mass transport (rOMT) analysis, however, information specific to glymphatic clearance was not directly derived. To fill this knowledge gap, we here implemented unbalanced rOMT analysis which allows for assessment of both influx and clearance. Dynamic influx/clearance brain maps were derived from rTg-DI rats with cerebral amyloid angiopathy (CAA) and TgSD-AD rats with Alzheimer’s disease (AD). The rTg-DI rats with severe CAA disease exhibited abnormal influx/clearance kinetics, while TgSD-AD rats with a moderate Aβ plaque load exhibited normal transport suggesting that different Aβ lesions and their overall burden differentially impact glymphatic system function.http://www.sciencedirect.com/science/article/pii/S2589004224026907Biological sciencesNeuroscience |
| spellingShingle | Sunil Koundal Xinan Chen Zachary Gursky Hedok Lee Kaiming Xu Feng Liang Zhongcong Xie Feng Xu Hung-Mo Lin William E. Van Nostrand Xianfeng Gu Rena Elkin Allen Tannenbaum Helene Benveniste Divergent brain solute clearance in rat models of cerebral amyloid angiopathy and Alzheimer’s disease iScience Biological sciences Neuroscience |
| title | Divergent brain solute clearance in rat models of cerebral amyloid angiopathy and Alzheimer’s disease |
| title_full | Divergent brain solute clearance in rat models of cerebral amyloid angiopathy and Alzheimer’s disease |
| title_fullStr | Divergent brain solute clearance in rat models of cerebral amyloid angiopathy and Alzheimer’s disease |
| title_full_unstemmed | Divergent brain solute clearance in rat models of cerebral amyloid angiopathy and Alzheimer’s disease |
| title_short | Divergent brain solute clearance in rat models of cerebral amyloid angiopathy and Alzheimer’s disease |
| title_sort | divergent brain solute clearance in rat models of cerebral amyloid angiopathy and alzheimer s disease |
| topic | Biological sciences Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224026907 |
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