Abstract
Cerebral small vessel disease (SVD) is a leading cause of stroke and dementia in the population. Hypertension is a key risk factor for the disease, and animal models have been widely utilized to elucidate the mechanisms by which elevated blood pressure impairs cerebrovascular structure and function to result in cognitive decline. Among the mechanisms identified, endothelial dysfunction and vascular inflammation are thought be key determinants of the condition. In this chapter we will describe the anatomy of the cerebral vasculature and the mechanisms that regulate cerebral perfusion paying particular attention to how hypertension affects each mechanism. Finally, we will discuss the knowledge gaps that currently exist in the field.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Horsburgh K, Wardlaw JM, van Agtmael T, Allan SM, Ashford MLJ, Bath PM, Brown R, Berwick J, Cader MZ, Carare RO, Davis JB, Duncombe J, Farr TD, Fowler JH, Goense J, Granata A, Hall CN, Hainsworth AH, Harvey A, Hawkes CA, Joutel A, Kalaria RN, Kehoe PG, Lawrence CB, Lockhart A, Love S, Macleod MR, Macrae IM, Markus HS, McCabe C, McColl BW, Meakin PJ, Miller A, Nedergaard M, O’Sullivan M, Quinn TJ, Rajani R, Saksida LM, Smith C, Smith KJ, Touyz RM, Trueman RC, Wang T, Williams A, Williams SCR, Work LM. Small vessels, dementia and chronic diseases – molecular mechanisms and pathophysiology. Clin Sci. 2018;132(8):851–68.
Joutel A, Faraci FM. Cerebral small vessel disease: insights and opportunities from mouse models of collagen IV-related small vessel disease and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke. 2014;45(4):1215–21.
De Silva TM, Faraci FM. Microvascular dysfunction and cognitive impairment. Cell Mol Neurobiol. 2016;36(2):241–58.
Yang Y, Kimura-Ohba S, Thompson J, Rosenberg GA. Rodent models of vascular cognitive impairment. Transl Stroke Res. 2016;7(5):407–14.
Kaiser D, Weise G, Möller K, Scheibe J, Pösel C, Baasch S, Gawlitza M, Lobsien D, Diederich K, Minnerup J, Kranz A, Boltze J, Wagner D-C. Spontaneous white matter damage, cognitive decline and neuroinflammation in middle-aged hypertensive rats: an animal model of early-stage cerebral small vessel disease. Acta Neuropathol Commun. 2014;2:169.
Pires PW, Dams Ramos CM, Matin N, Dorrance AM. The effects of hypertension on the cerebral circulation. Am J Physiol Heart Circ Physiol. 2013;304(12):H1598–614.
Faraco G, Park L, Anrather J, Iadecola C. Brain perivascular macrophages: characterization and functional roles in health and disease. J Mol Med. 2017;95(11):1143–52.
Diaz-Otero JM, Fisher C, Downs K, Moss ME, Jaffe IZ, Jackson WF, Dorrance AM. Endothelial mineralocorticoid receptor mediates parenchymal arteriole and posterior cerebral artery remodeling during angiotensin II-induced hypertension. Hypertension. 2017;70(6):1113–21.
Diaz-Otero JM, Yen T-C, Fisher C, Bota D, Jackson WF Dorrance AM. Mineralocorticoid receptor antagonism improves parenchymal arteriole dilation via a TRPV4-dependent mechanism and prevents cognitive dysfunction in hypertension. Am J Physiol Heart Circ Physiol. 2018;315(5):H1304–H1315.
Hainsworth AH, Allan SM, Boltze J, Cunningham C, Farris C, Head E, Ihara M, Isaacs JD, Kalaria RN, Lesnik Oberstein SAMJ, Moss MB, Nitzsche B, Rosenberg GA, Rutten JW, Salkovic-Petrisic M, Troen AM. Translational models for vascular cognitive impairment: a review including larger species. BMC Med. 2017;15(1):16.
Dabertrand F, Krøigaard C, Bonev AD, Cognat E, Dalsgaard T, Domenga-Denier V, Hill-Eubanks DC, Brayden JE, Joutel A, Nelson MT. Potassium channelopathy-like defect underlies early-stage cerebrovascular dysfunction in a genetic model of small vessel disease. Proc Natl Acad Sci U S A. 2015;112(7):E796–805.
Taylor ZJ, Hui ES, Watson AN, Nie X, Deardorff RL, Jensen JH, Helpern JA, Shih AY. Microvascular basis for growth of small infarcts following occlusion of single penetrating arterioles in mouse cortex. J Cereb Blood Flow Metab. 2016;36(8):1357–73.
Iadecola C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron. 2017;96(1):17–42.
Gould IG, Tsai P, Kleinfeld D, Linninger A. The capillary bed offers the largest hemodynamic resistance to the cortical blood supply. J Cereb Blood Flow Metab. 2017;37(1):52–68.
Pires PW, Jackson WF, Dorrance AM. Regulation of myogenic tone and structure of parenchymal arterioles by hypertension and the mineralocorticoid receptor. Am J Physiol Heart Circ Physiol. 2015;309(1):H127–36.
Guerra G, Lucariello A, Perna A, Botta L, De Luca A Moccia F. The role of endothelial Ca2+ signaling in neurovascular coupling: a view from the lumen. Int J Mol Sci. 2018;19(4).
Santisteban MM, Iadecola C. Hypertension, dietary salt and cognitive impairment. J Cereb Blood Flow Metab. 2018;38(12):2112–28.
Calcinaghi N, Wyss MT, Jolivet R, Singh A, Keller AL, Winnik S, Fritschy J-M, Buck A, Matter CM, Weber B. Multimodal imaging in rats reveals impaired neurovascular coupling in sustained hypertension. Stroke. 2013;44(7):1957–64.
Faraco G, Sugiyama Y, Lane D, Garcia-Bonilla L, Chang H, Santisteban MM, Racchumi G, Murphy M, Van Rooijen N, Anrather J, Iadecola C. Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension. J Clin Invest. 2016;126(12):4674–89.
Bosetti F, Galis ZS, Bynoe MS, Charette M, Cipolla MJ, Del Zoppo GJ, Gould D, Hatsukami TS, Jones TLZ, Koenig JI, Lutty GA, Maric-Bilkan C, Stevens T, Tolunay HE, Koroshetz W, “Small Blood Vessels: Big Health Problems” Workshop Participants. “Small blood vessels: big health problems?”: scientific recommendations of the national institutes of health workshop. J Am Heart Assoc. 2016;5(11).
Hu X, De Silva TM, Chen J, Faraci FM. Cerebral vascular disease and neurovascular injury in ischemic stroke. Circ Res. 2017;120(3):449–71.
Faraco G, Brea D, Garcia-Bonilla L, Wang G, Racchumi G, Chang H, Buendia I, Santisteban MM, Segarra SG, Koizumi K, Sugiyama Y, Murphy M, Voss H, Anrather J, Iadecola C. Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat Neurosci. 2018;21(2):240–9.
Jessen NA, Munk ASF, Lundgaard I, Nedergaard M. The glymphatic system: a beginner’s guide. Neurochem Res. 2015;40(12):2583–99.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Dorrance, A.M., Abolibdeh, B., Diaz-Otero, J.M. (2019). Cerebral Small Vessel Disease and Vascular Cognitive Impairment: Preclinical Aspects. In: Touyz, R., Delles, C. (eds) Textbook of Vascular Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-16481-2_26
Download citation
DOI: https://doi.org/10.1007/978-3-030-16481-2_26
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-16480-5
Online ISBN: 978-3-030-16481-2
eBook Packages: MedicineMedicine (R0)