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1663-4365132021Frontiers in aging neuroscienceFront Aging NeurosciImpaired Glymphatic Function and Pulsation Alterations in a Mouse Model of Vascular Cognitive Impairment.78851978851978851910.3389/fnagi.2021.788519Large vessel disease and carotid stenosis are key mechanisms contributing to vascular cognitive impairment (VCI) and dementia. Our previous work, and that of others, using rodent models, demonstrated that bilateral common carotid stenosis (BCAS) leads to cognitive impairment via gradual deterioration of the neuro-glial-vascular unit and accumulation of amyloid-β (Aβ) protein. Since brain-wide drainage pathways (glymphatic) for waste clearance, including Aβ removal, have been implicated in the pathophysiology of VCI via glial mechanisms, we hypothesized that glymphatic function would be impaired in a BCAS model and exacerbated in the presence of Aβ. Male wild-type and Tg-SwDI (model of microvascular amyloid) mice were subjected to BCAS or sham surgery which led to a reduction in cerebral perfusion and impaired spatial learning acquisition and cognitive flexibility. After 3 months survival, glymphatic function was evaluated by cerebrospinal fluid (CSF) fluorescent tracer influx. We demonstrated that BCAS caused a marked regional reduction of CSF tracer influx in the dorsolateral cortex and CA1-DG molecular layer. In parallel to these changes increased reactive astrogliosis was observed post-BCAS. To further investigate the mechanisms that may lead to these changes, we measured the pulsation of cortical vessels. BCAS impaired vascular pulsation in pial arteries in WT and Tg-SwDI mice. Our findings show that BCAS influences VCI and that this is paralleled by impaired glymphatic drainage and reduced vascular pulsation. We propose that these additional targets need to be considered when treating VCI.Copyright © 2022 Li, Kitamura, Beverley, Koudelka, Duncombe, Lennen, Jansen, Marshall, Platt, Wiegand, Carare, Kalaria, Iliff and Horsburgh.LiMosiMCentre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.Edinburgh Medical School, UK Dementia Research Institute, University of Edinburgh, Edinburgh, United Kingdom.KitamuraAkihiroACentre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.Department of Neurology, Shiga University of Medical Science, Otsu, Japan.BeverleyJoshuaJCentre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.KoudelkaJurajJCentre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.DuncombeJessicaJCentre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.LennenRossRCentre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.JansenMaurits AMACentre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.MarshallIanICentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.PlattBettinaBSchool of Medicine, Medical Sciences and Nutrition, College of Life Sciences and Medicine, University of Aberdeen, Aberdeen, United Kingdom.WiegandUlrich KUKCentre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.CarareRoxana OROFaculty of Medicine, University of Southampton, Southampton, United Kingdom.KalariaRajesh NRNTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.IliffJeffrey JJJVISN 20 Mental Illness Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States.Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, United States.Department of Neurology, University of Washington School of Medicine, Seattle, WA, United States.HorsburghKarenKCentre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.engMR/K015710/1MRC_Medical Research CouncilUnited KingdomR01 AG054456AGNIA NIH HHSUnited StatesJournal Article20220113
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1426501MCID_676f08607e30e463e609d98f 39725239 39721674 39721217 39720539 39719574 function "functional"[All Fields] OR "functional's"[All Fields] OR "functionalities"[All Fields] OR "functionality"[All Fields] OR "functionalization"[All Fields] OR "functionalizations"[All Fields] OR "functionalize"[All Fields] OR "functionalized"[All Fields] OR "functionalizes"[All Fields] OR "functionalizing"[All Fields] OR "functionally"[All Fields] OR "functionals"[All Fields] OR "functioned"[All Fields] OR "functioning"[All Fields] OR "functionings"[All Fields] OR "functions"[All Fields] OR "physiology"[Subheading] OR "physiology"[All Fields] OR "function"[All Fields] OR "physiology"[MeSH Terms] "glymphatic"[All Fields] AND ("functional"[All Fields] OR "functional s"[All Fields] OR "functionalities"[All Fields] OR "functionality"[All Fields] OR "functionalization"[All Fields] OR "functionalizations"[All Fields] OR "functionalize"[All Fields] OR "functionalized"[All Fields] OR "functionalizes"[All Fields] OR "functionalizing"[All Fields] OR "functionally"[All Fields] OR "functionals"[All Fields] OR "functioned"[All Fields] OR "functioning"[All Fields] OR "functionings"[All Fields] OR "functions"[All Fields] OR "physiology"[MeSH Subheading] OR "physiology"[All Fields] OR "function"[All Fields] OR "physiology"[MeSH Terms]) trying2...
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1873-27472024Dec24Brain research bulletinBrain Res BullCognitive disorders: potential astrocyte-based mechanism.11118111118110.1016/j.brainresbull.2024.111181S0361-9230(24)00315-0Cognitive disorders are a common clinical manifestation, including a deterioration in the patient's memory ability, attention, executive power, language, and other functions. The contributing factors of cognitive disorders are numerous and diverse in nature, including organic diseases and other mental disorders. Neurodegenerative diseases are a common type of organic disease related to the pathology of neuronal death and disruption of glial cell balance, ultimately accompanied with cognitive impairment. Thus, cognitive disorder frequently serves as an extremely critical indicator of neurodegenerative disorders. Cognitive impairments negatively affect patients' daily lives. However, our understanding of the precise pathogenic pathways of cognitive defects remains incomplete. The most prevalent kind of glial cells in the central nervous system are called astrocytes. They have a unique significance in cerebral function because of their wide range of functions in maintaining homeostasis in the central nervous system, regulating synaptic plasticity, and so on. Dysfunction of astrocytes is intimately linked to cognitive disorders, and we are attempting to understand this phenomenon predominantly from those perspectives: neuroinflammation, astrocytic senescence, connexin, Ca2+ signaling, mitochondrial dysfunction, and the glymphatic system.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.LiShiyuSDepartment of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.ChenYeruYDepartment of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.ChenGangGDepartment of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: China.chengang120@zju.edu.cn.engJournal ArticleReview20241224
United StatesBrain Res Bull76058180361-9230IMastrocytic homeostasiscognitionDeclaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.202482520241211202412232024122702120241227021202412261918aheadofprint3972523910.1016/j.brainresbull.2024.111181S0361-9230(24)00315-0397216742024122520241225
1099-14923822025FebNMR in biomedicineNMR BiomedEvaluation of the Glymphatic System in Rabbits Using Gadobutrol-Enhanced MR Cisternography With T1 and T2 Mapping.e5314e531410.1002/nbm.5314We aimed to characterize and further understand CSF circulation and outflow of rabbits. To our knowledge, there is no research on contrast material-enhanced MR cisternography (CE-MRC) with T1 and T2 mapping in the rabbit model using a clinical 3-T MR unit without a stereotaxic frame.Twenty-one rabbits were included in the study. The CE-MRC exams with T1/T2 mappings were categorized into approximate time points based on an intention-to-scan approach: precontrast, less than 4 h after contrast, 24 h after contrast, and 24 to 120 h after gadobutrol. The presence of contrast media in the head and neck structures was scored with a 3-point scale (present, score: 2; absent, score: 0; and inconsistent, score: 1). T1 and T2 estimates were directly derived by drawing regions of interest on the corresponding maps.Gadobutrol accumulation was detected in the CSF near the cribriform plate and nasal areas on early-phase postcontrast images of all animals. These contrast material accumulations completely disappeared on the images obtained in postcontrast ≥ 24 h. The lowest T1 and T2 estimates in olfactory and cerebral areas were observed on early-phase images. Significant correlations were observed between the enhancement of the bladder and the medial portion of the sclera and the enhancement of inner ear structures, olfactory regions, turbinates, nasal cavities, and cranial subarachnoid spaces. The T1 and T2 estimates of the septum and olfactory bulb were generally lower than those measured in the frontal and parietal lobes on early-phase images.Our findings, which indicate an absence of clearly visible arachnoid granulations in rabbits, support the significance of olfactory outflow and the glymphatic system as highlighted in recent literature. Glymphatic transport can be more effectively demonstrated using T1 mapping in rabbits. The anatomical and physiological differences between human and rodent central nervous systems must be considered when translating experimental results from rabbits to humans.© 2024 John Wiley & Sons Ltd.AlginOktayO0000-0002-3877-8366Department of Radiology, Medical Faculty, Ankara University, Ankara, Türkiye.Interventional MR Clinical R&D Institute, Ankara University, Ankara, Altındag, Türkiye.National MR Research Center, Bilkent University, Ankara, Türkiye.CetinkayaKadirKNeurosurgery Department, Tokat Government Hospital, Tokat, Türkiye.OtoCagdasCDepartment of Radiology, Medical Faculty, Ankara University, Ankara, Türkiye.Interventional MR Clinical R&D Institute, Ankara University, Ankara, Altındag, Türkiye.National MR Research Center, Bilkent University, Ankara, Türkiye.Department of Anatomy, Veterinary Faculty, Ankara University, Ankara, Türkiye.AyberkGıyasGNeurosurgery Department, Medical Faculty, Yıldırım Beyazıt University, Ankara, Türkiye.engJournal Article
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Scheyhing, et al., “Human Brain Clearance Imaging: Pathways Taken by Magnetic Resonance Imaging Contrast Agents After Administration in Cerebrospinal Fluid and Blood,” NMR in Biomedicine 37, no. 9 (2024): e5159.D. Jiang, Y. Gou, Z. Wei, X. Hou, V. Yedavalli, and H. Lu, “Quantification of T1 and T2 of Subarachnoid CSF: Implications for Water Exchange Between CSF and Brain Tissues,” Magnetic Resonance in Medicine 90, no. 6 (2023): 2411–2419.X. Miao, A. G. Paez, S. Rajan, et al., “Functional Activities Detected in the Olfactory Bulb and Associated Olfactory Regions in the Human Brain Using T2‐Prepared BOLD Functional MRI at 7T,” Frontiers in Neuroscience 15 (2021): 723441.O. Algin, U. Koc, and G. Ayberk, “Feasibility of 3D T1W Sequences in Contrast‐Material Enhanced MR Cisternography at 3T,” Turkish Journal of Medical Sciences 52, no. 6 (2022): 1943–1949.A. M. Sweeney, V. Plá, T. Du, et al., “In Vivo Imaging of Cerebrospinal Fluid Transport Through the Intact Mouse Skull Using Fluorescence Macroscopy,” Journal of Visualized Experiments no. 149 (2019): e59774, https://doi.org/10.3791/59774.3972121720241225
2352-39641112024Dec24EBioMedicineEBioMedicineRobust, fully-automated assessment of cerebral perivascular spaces and white matter lesions: a multicentre MRI longitudinal study of their evolution and association with risk of dementia and accelerated brain atrophy.10552310552310.1016/j.ebiom.2024.105523S2352-3964(24)00559-0Perivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. However, it is unknown whether PVS can predict dementia risk and brain atrophy trajectories in participants without dementia, as longitudinal studies on PVS are scarce and current methods for PVS assessment lack robustness and inter-scanner reproducibility.We developed a robust algorithm to automatically assess PVS count and size on clinical MRI, and investigated 1) their relationship with dementia risk and brain atrophy in participants without dementia, 2) their longitudinal evolution, and 3) their potential use as a screening tool in simulated clinical trials. We analysed 46,478 clinical measurements of cognitive functioning and 20,845 brain MRI scans from 10,004 participants (71.1 ± 9.7 years-old, 56.6% women) from three publicly available observational studies on ageing and dementia (the Alzheimer's Disease Neuroimaging Initiative, the National Alzheimer's Coordinating Centre database, and the Open Access Series of Imaging Studies). Clinical and MRI data collected between 2004 and 2022 were analysed with consistent methods, controlling for confounding factors, and combined using mixed-effects models.Our fully-automated method for PVS assessment showed excellent inter-scanner reproducibility (intraclass correlation coefficients >0.8). Fewer PVS and larger PVS diameter at baseline predicted higher dementia risk and accelerated brain atrophy. Longitudinal trajectories of PVS markers differed significantly in participants without dementia who converted to dementia compared with non-converters. In simulated placebo-controlled trials for treatments targeting cognitive decline, screening out participants at low risk of dementia based on our PVS markers enhanced the power of the trial independently of Alzheimer's disease biomarkers.These robust cerebrovascular markers predict dementia risk and brain atrophy and may improve risk-stratification of patients, potentially reducing cost and increasing throughput of clinical trials to combat dementia.US National Institutes of Health.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.BarisanoGiuseppeGDepartment of Neurosurgery, Stanford University, Stanford, CA, USA. Electronic address: barisano@stanford.edu.IvMichaelMDepartment of Radiology, Stanford University, Stanford, CA, USA.ChoupanJeiranJLaboratory of Neuro Imaging, University of Southern California, Los Angeles, CA, USA; NeuroScope Inc., New York, NY, USA.Hayden-GephartMelanieMDepartment of Neurosurgery, Stanford University, Stanford, CA, USA.Alzheimer’s Disease Neuroimaging InitiativeengJournal Article20241224
NetherlandsEBioMedicine1016470392352-3964IMAlzheimer’s diseaseDementiaGlymphatic systemPerivascular spacesSmall vessel diseaseWhite matter lesionsDeclaration of interests Giuseppe Barisano is listed as inventor on a patent application related to this work filed by Stanford University. The other authors declare that they have no competing interests. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Ageing, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.WeinerMichaelMAisenPaulPPetersenRonaldRJackClifford RCRJagustWilliamWTrojanowkiJohn QJQTogaArthur WAWBeckettLaurelLGreenRobert CRCSaykinAndrew JAJMorrisJohnJShawLeslie MLMLiuEnchiEMontineTomTThomasRonald GRGDonohueMichaelMWalterSarahSGessertDevonDSatherTamieTJiminezGusGHarveyDanielleDDonohueMichaelMBernsteinMatthewMFoxNickNThompsonPaulPSchuffNorbertNDeCarliCharlesCBorowskiBretBGunterJeffJSenjemMattMVemuriPrashanthiPJonesDavidDKantarciKejalKWardChadCKoeppeRobert ARAFosterNormNReimanEric MEMChenKeweiKMathisChetCLandauSusanSCairnsNigel JNJHouseholderErinEReinwaldLisa TaylorLTLeeVirginiaVKoreckaMagdalenaMFigurskiMichalMCrawfordKarenKNeuScottSForoudTatiana MTMPotkinStevenSShenLiLKelleyFaberFKimSungeunSNhoKwangsikKKachaturianZavenZFrankRichardRSnyderPeter JPJMolchanSusanSKayeJeffreyJQuinnJosephJLindBettyBCarterRainaRDolenSaraSSchneiderLon SLSPawluczykSoniaSBecceraMauricioMTeodoroLibertyLSpannBryan MBMBrewerJamesJVanderswagHelenHFleisherAdamAHeidebrinkJudith LJLLordJoanne LJLPetersenRonaldRMasonSara SSSAlbersColleen SCSKnopmanDavidDJohnsonKrisKDoodyRachelle SRSMeyerJavier VillanuevaJVChowdhuryMunirMRountreeSusanSDangMimiMSternYaakovYHonigLawrence SLSBellKaren LKLAncesBeauBMorrisJohn CJCCarrollMariaMLeonSueSHouseholderErinEMintunMark AMASchneiderStacySOliverAngelaAMarsonDanielDGriffithRandallRClarkDavidDGeld-MacherDavidDBrockingtonJohnJRobersonErikEGrossmanHillelHMitsisEffieELeyla deToledo-MorrellShahRaj CRCDuaraRanjanRVaronDanielDGreigMaria TMTRobertsPeggyPAlbertMarilynMOnyikeChiadiCD'AgostinoDanielDKielbStephanieSGalvinJames EJEPogorelecDana MDMCerboneBrittanyBMichelChristina ACARusinekHenryHde LeonMony JMJGlodzikLidiaLDe SantiSusanSDoraiswamyP MuraliPMPetrellaJeffrey RJRWongTerence ZTZArnoldSteven ESEKarlawishJason HJHWolkDavidDSmithCharles DCDJichaGregGHardyPeterPSinhaParthaPOatesElizabethEConradGaryGLopezOscar LOLOakleyMaryAnnMSimpsonDonna MDMPorsteinssonAnton PAPGoldsteinBonnie SBSMartinKimKMakinoKelly MKMIsmailM SaleemMSBrandConnieCMulnardRuth ARAThaiGabyGAdams OrtizCatherine McCMWomackKyleKMathewsDanaDQuicenoMaryMArrastiaRamon DiazRDKingRichardRWeinerMyronMCookKristen MartinKMDeVousMichaelMLeveyAllan IAILahJames JJJCellarJanet SJSBurnsJeffrey MJMAndersonHeather SHSSwerdlowRussell HRHApostolovaLianaLTingusKathleenKWooEllenESilvermanDaniel H SDHSLuPo HPHBartzokisGeorgeGGraff RadfordNeill RNRParfittFrancineFKendallTracyTJohnsonHeatherHFarlowMartin RMRHakeAnnMarieAMatthewsBrandy RBRHerringScottSHuntCynthiaCvan DyckChristopher HCHCarsonRichard EREMacAvoyMartha GMGChertkowHowardHBergmanHowardHHoseinChrisCBlackSandraSStefanovicBojanaBCaldwellCurtisCRobin HsiungGing-YuekGYFeldmanHowardHMudgeBenitaBAssalyMicheleMKerteszAndrewARogersJohnJTrostDickDBernickCharlesCMunicDonnaDKerwinDianaDMesulamMarek MarselMMLipowskiKristineKWuChuang KuoCKJohnsonNancyNSadowskyCarlCMartinezWalterWVillenaTeresaTTurnerRaymond ScottRSJohnsonKathleenKReynoldsBrigidBSperlingReisa ARAJohnsonKeith AKAMarshallGadGFreyMeghanMYesavageJeromeJTaylorJoy LJLLaneBartonBRosenAllysonATinklenbergJaredJSabbaghMarwan NMNBeldenChristine MCMJacobsonSandra ASASirrelSherye ASAKowallNeilNKillianyRonaldRBudsonAndrew EAENorbashAlexanderAJohnsonPatricia LynnPLObisesanThomas OTOWoldaySabaSAllardJoanneJLernerAlanAOgrockiPaulaPHudsonLeonLFletcherEvanECarmichaelOwenOOlichneyJohnJDeCarliCharlesCKitturSmitaSBorrieMichaelMLeeT YTYBarthaRobRJohnsonSterlingSAsthanaSanjaySCarlssonCynthia MCMPotkinSteven GSGPredaAdrianANguyenDanaDTariotPierrePFleisherAdamAReederStephanieSBatesVerniceVCapoteHoracioHRainkaMichelleMScharreDouglas WDWKatakiMariaMAdeliAnahitaAZimmermanEarl AEACelminsDzintraDBrownAlice DADPearlsonGodfrey DGDBlankKarenKAndersonKarenKSantulliRobert BRBKitzmillerTamar JTJSchwartzEben SESSinkKaycee MKMWilliamsonJeff DJDGargPradeepPWatkinsFranklinFOttBrian RBRQuerfurthHenryHTremontGeoffreyGSallowayStephenSMalloyPaulPCorreiaStephenSRosenHoward JHJMillerBruce LBLMintzerJacoboJSpicerKennethKBachmanDavidDFingerElizabethEPasternakStephenSRachinskyIrinaIRogersJohnJKerteszAndrewADrostDickDPomaraNunzioNHernandoRaymundoRSarraelAnteroASchultzSusan KSKBoles PontoLaura LLLShimHyungsubHSmithKaren ElizabethKERelkinNormanNChaingGloriaGRaudinLisaLSmithAmandaAFargherKristinKRajBalebail AshokBA2024729202411320241210202412260202024122602020241225185aheadofprint3972121710.1016/j.ebiom.2024.105523S2352-3964(24)00559-03972053920241225
2589-004227122024Dec20iScienceiScienceDivergent brain solute clearance in rat models of cerebral amyloid angiopathy and Alzheimer's disease.11146311146311146310.1016/j.isci.2024.111463Brain 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.© 2024 The Author(s).KoundalSunilSDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT 06510, USA.ChenXinanXDepartment of Medical Physics, Memorial Sloan Kettering Cancer Center, New York City, NY 10065, USA.GurskyZacharyZDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT 06510, USA.LeeHedokHDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT 06510, USA.XuKaimingKDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT 06510, USA.Department of Applied Mathematics & Statistics, Stony Brook University, Stony Brook, NY 11794, USA.LiangFengFDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA.XieZhongcongZDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA.XuFengFGeorge and Anne Ryan Institute for Neuroscience and the Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02906, USA.LinHung-MoHMDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT 06510, USA.Van NostrandWilliam EWEGeorge and Anne Ryan Institute for Neuroscience and the Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02906, USA.GuXianfengXDepartment of Applied Mathematics & Statistics, Stony Brook University, Stony Brook, NY 11794, USA.Departments of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA.ElkinRenaRDepartment of Medical Physics, Memorial Sloan Kettering Cancer Center, New York City, NY 10065, USA.TannenbaumAllenADepartment of Applied Mathematics & Statistics, Stony Brook University, Stony Brook, NY 11794, USA.Departments of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA.BenvenisteHeleneHDepartment 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.engJournal Article20241123
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Impaired Glymphatic Function and Pulsation Alterations in a Mouse Model of Vascular Cognitive Impairment. | LitMetric
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Impaired Glymphatic Function and Pulsation Alterations in a Mouse Model of Vascular Cognitive Impairment.

Mosi Li Akihiro Kitamura Joshua Beverley Juraj Koudelka Jessica Duncombe Ross Lennen Maurits A Jansen Ian Marshall Bettina Platt Ulrich K Wiegand Roxana O Carare Rajesh N Kalaria Jeffrey J Iliff Karen Horsburgh

Front Aging Neurosci

Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.

Published: January 2022

Large vessel disease and carotid stenosis are key mechanisms contributing to vascular cognitive impairment (VCI) and dementia. Our previous work, and that of others, using rodent models, demonstrated that bilateral common carotid stenosis (BCAS) leads to cognitive impairment via gradual deterioration of the neuro-glial-vascular unit and accumulation of amyloid-β (Aβ) protein. Since brain-wide drainage pathways (glymphatic) for waste clearance, including Aβ removal, have been implicated in the pathophysiology of VCI via glial mechanisms, we hypothesized that glymphatic function would be impaired in a BCAS model and exacerbated in the presence of Aβ. Male wild-type and Tg-SwDI (model of microvascular amyloid) mice were subjected to BCAS or sham surgery which led to a reduction in cerebral perfusion and impaired spatial learning acquisition and cognitive flexibility. After 3 months survival, glymphatic function was evaluated by cerebrospinal fluid (CSF) fluorescent tracer influx. We demonstrated that BCAS caused a marked regional reduction of CSF tracer influx in the dorsolateral cortex and CA1-DG molecular layer. In parallel to these changes increased reactive astrogliosis was observed post-BCAS. To further investigate the mechanisms that may lead to these changes, we measured the pulsation of cortical vessels. BCAS impaired vascular pulsation in pial arteries in WT and Tg-SwDI mice. Our findings show that BCAS influences VCI and that this is paralleled by impaired glymphatic drainage and reduced vascular pulsation. We propose that these additional targets need to be considered when treating VCI.

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