Impaired Glymphatic Transport in Spontaneously Hypertensive Rats.
Age Factors
Alzheimer Disease
/ physiopathology
Animals
Cerebral Ventricles
/ pathology
Cerebrospinal Fluid
/ physiology
Contrast Media
/ pharmacokinetics
Disease Progression
Glymphatic System
/ physiopathology
Heterocyclic Compounds
/ cerebrospinal fluid
Hypertension
/ physiopathology
Magnetic Resonance Imaging
/ methods
Male
Organ Size
Organometallic Compounds
/ cerebrospinal fluid
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Rheology
CSF transport kinetics
contrast agent
middle cerebral artery
perivascular spaces
small vessel disease
volumetric MR
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
Titre abrégé: J Neurosci
Pays: United States
ID NLM: 8102140
Informations de publication
Date de publication:
07 08 2019
07 08 2019
Historique:
received:
31
07
2018
revised:
31
03
2019
accepted:
30
05
2019
pubmed:
19
6
2019
medline:
26
6
2020
entrez:
19
6
2019
Statut:
ppublish
Résumé
The glymphatic system is a brainwide CSF transport system that uses the perivascular space for fast inflow of CSF. Arterial pulsations are a major driver of glymphatic CSF inflow, and hypertension that causes vascular pathologies, such as arterial stiffening and perivascular alterations, may impede the inflow. We used dynamic contrast-enhanced MRI to assess the effect of hypertension on glymphatic transport kinetics in male young and adult spontaneously hypertensive (SHR) rats compared with age-matched normotensive Wistar-Kyoto rats (WKY). We anesthetized the rats with dexmedetomidine/isoflurane and infused paramagnetic contrast (Gd-DOTA) into the cisterna magna during dynamic contrast-enhanced MRI to quantify glymphatic transport kinetics. Structural MRI analysis showed that cerebroventricular volumes are larger and brain volumes significantly smaller in SHR compared with WKY rats, regardless of age. We observed ventricular reflux of Gd-DOTA in SHR rats only, indicating abnormal CSF flow dynamics secondary to innate hydrocephalus. One-tissue compartment analysis revealed impeded glymphatic transport of Gd-DOTA in SHR compared with WKY rats in both age groups, implying that glymphatic transport, including solute clearance from brain parenchyma, is impaired during evolving hypertension in young SHR, an effect that worsens in states of chronic hypertension. The study demonstrates the suppression of glymphatic clearance in SHR rats and thus offers new insight into the coexistence of hypertension and concomitant vascular pathologies in Alzheimer's disease. The study further highlights the importance of considering the distribution of tracers in the CSF compartment in the analysis of the glymphatic system.
Identifiants
pubmed: 31209176
pii: JNEUROSCI.1974-18.2019
doi: 10.1523/JNEUROSCI.1974-18.2019
pmc: PMC6687896
doi:
Substances chimiques
Contrast Media
0
Heterocyclic Compounds
0
Organometallic Compounds
0
gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
99J2XUF1JT
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6365-6377Subventions
Organisme : NIA NIH HHS
ID : R01 AG048769
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NINDS NIH HHS
ID : RF1 NS110049
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS100366
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG057575
Pays : United States
Informations de copyright
Copyright © 2019 the authors.
Références
Childs Nerv Syst. 1999 Sep;15(9):461-7
pubmed: 10502007
J Neurol. 2000 Jan;247(1):5-14
pubmed: 10701891
Neuroscience. 2000;100(2):251-8
pubmed: 11008165
Arch Neurol. 2001 Mar;58(3):397-405
pubmed: 11255443
Mech Ageing Dev. 2002 Mar 15;123(5):547-59
pubmed: 11796140
Jpn Circ J. 1963 Mar;27:282-93
pubmed: 13939773
Circulation. 2003 Sep 23;108(12):1527-32
pubmed: 14504252
Circ Res. 1992 Jul;71(1):145-58
pubmed: 1535029
Diabet Med. 1992 Mar;9(2):114-9
pubmed: 1563244
Lancet Neurol. 2005 Aug;4(8):487-99
pubmed: 16033691
Histol Histopathol. 2006 Feb;21(2):179-85
pubmed: 16329042
Mol Ther. 2006 Jul;14(1):69-78
pubmed: 16650807
Cell Metab. 2008 Jun;7(6):476-84
pubmed: 18522829
Brain Res. 2010 Apr 14;1325:155-63
pubmed: 20156423
IEEE Trans Med Imaging. 2010 Jun;29(6):1310-20
pubmed: 20378467
Lancet Neurol. 2010 Jul;9(7):689-701
pubmed: 20610345
Neuroimage. 2011 Feb 1;54(3):2033-44
pubmed: 20851191
Vasc Med. 2010 Dec;15(6):461-8
pubmed: 21056945
J Neuropathol Exp Neurol. 2010 Dec;69(12):1201-9
pubmed: 21107133
IEEE Trans Image Process. 2011 Sep;20(9):2554-64
pubmed: 21411404
Neuroimage. 2011 Sep 1;58(1):75-81
pubmed: 21708273
Sci Transl Med. 2012 Aug 15;4(147):147ra111
pubmed: 22896675
J Clin Invest. 2013 Mar;123(3):1299-309
pubmed: 23434588
Lancet Neurol. 2013 May;12(5):483-97
pubmed: 23602162
Physiol Res. 2013;62(5):471-8
pubmed: 24020816
Circ Res. 1990 Jan;66(1):8-17
pubmed: 2403863
J Neurosci. 2013 Nov 13;33(46):18190-9
pubmed: 24227727
Neuroimage. 2014 Aug 15;97:374-86
pubmed: 24726336
Hypertension. 2014 Aug;64(2):210-4
pubmed: 24799614
Ann Neurol. 2014 Dec;76(6):845-61
pubmed: 25204284
Hypertension. 1989 Aug;14(2):191-202
pubmed: 2527201
J Neurosci. 2014 Dec 3;34(49):16180-93
pubmed: 25471560
Acta Neuropathol Commun. 2014 Dec 18;2:169
pubmed: 25519173
J Neurosci. 2015 Jan 14;35(2):518-26
pubmed: 25589747
J Cereb Blood Flow Metab. 2015 Jun;35(6):1005-14
pubmed: 25669904
Nature. 2015 Jul 16;523(7560):337-41
pubmed: 26030524
J Exp Med. 2015 Jun 29;212(7):991-9
pubmed: 26077718
J Neurosci. 2015 Aug 5;35(31):11034-44
pubmed: 26245965
Stroke. 2015 Nov;46(11):3039-40
pubmed: 26504189
Mol Neurodegener. 2015 Nov 02;10:58
pubmed: 26526066
J Cereb Blood Flow Metab. 2016 Jun;36(6):1033-45
pubmed: 26690495
Magn Reson Med. 2017 Jan;77(1):398-410
pubmed: 26778056
Can J Cardiol. 2016 May;32(5):680-686.e4
pubmed: 27118295
Physiol Rep. 2016 May;4(10):null
pubmed: 27233301
Neurobiol Dis. 2016 Sep;93:215-25
pubmed: 27234656
Exp Anim. 2016 Nov 1;65(4):393-402
pubmed: 27301719
J Cereb Blood Flow Metab. 2017 Apr;37(4):1326-1337
pubmed: 27306755
Acta Neurol Scand. 2017 May;135(5):576-584
pubmed: 27388230
JAMA Neurol. 2017 Jan 1;74(1):91-99
pubmed: 27893874
Sci Rep. 2017 Apr 7;7(1):744
pubmed: 28389645
Magn Reson Med. 2018 Mar;79(3):1568-1578
pubmed: 28627037
Elife. 2017 Aug 21;6:
pubmed: 28826498
Anesthesiology. 2017 Dec;127(6):976-988
pubmed: 28938276
Brain. 2017 Oct 1;140(10):2691-2705
pubmed: 28969373
Invest Ophthalmol Vis Sci. 2017 Sep 1;58(11):4784-4791
pubmed: 28973323
Sci Rep. 2017 Nov 22;7(1):15979
pubmed: 29167492
MethodsX. 2017 Nov 10;4:498-507
pubmed: 29872639
JCI Insight. 2018 Jul 12;3(13):
pubmed: 29997300
Hypertension. 1988 Aug;12(2):89-95
pubmed: 3044994
Nat Commun. 2018 Nov 19;9(1):4878
pubmed: 30451853
Elife. 2018 Dec 18;7:
pubmed: 30561329
Neuroimage. 2019 Mar;188:616-627
pubmed: 30578928
Anesthesiology. 1987 Jun;66(6):798-804
pubmed: 3592278
Brain Res. 1986 Apr 9;370(2):327-32
pubmed: 3708330
Brain Res. 1985 Feb 4;326(1):47-63
pubmed: 3971148
Hypertension. 1993 Jan;21(1):105-11
pubmed: 8418018
Magn Reson Med. 1996 Feb;35(2):246-51
pubmed: 8622590
Hypertension. 1997 Mar;29(3):736-43
pubmed: 9052889
J Clin Invest. 1997 Mar 1;99(5):1016-27
pubmed: 9062360
Hypertension. 1998 Aug;32(2):346-50
pubmed: 9719065
Cardiovasc Res. 1998 Jul;39(1):89-105
pubmed: 9764192