Impact of Stalling Events on Microcirculatory Hemodynamics in the Aged Brain

Overview

Journal Microcirculation

Specialties Biology
Cardiology & Vascular Diseases

Date 2024 Jan 24

PMID 38265175

Authors

Mohammad Jamshidi

Thomas Ventimiglia

Patrice Sudres

Cong Zhang

Frederic Lesage

William Rooney

Daniel Schwartz

Andreas A Linninger

Affiliations

Soon will be listed here.

Abstract

Objective: The role of cerebral microvasculature in cognitive dysfunction can be investigated by identifying the impact of blood flow on cortical tissue oxygenation. In this paper, the impact of capillary stalls on microcirculatory characteristics such as flow and hematocrit (Ht) in the cortical angioarchitecture is studied.

Methods: Using a deterministic mathematical model to simulate blood flow in a realistic mouse cortex, hemodynamics parameters, including pressure, flow, vessel diameter-adjustable hematocrit, and transit time are calculated as a function of stalling events.

Results: Using a non-linear plasma skimming model, it is observed that Ht increases in the penetrating arteries from the pial vessels as a function of cortical depth. The incidence of stalling on Ht distribution along the blood network vessels shows reduction of RBCs around the tissue near occlusion sites and decreased Ht concentration downstream from the blockage points. Moreover, upstream of the occlusion, there is a noticeable increase of the Ht, leading to larger flow resistance due to higher blood viscosity. We predicted marked changes in transit time behavior due to stalls which match trends observed in mice in vivo.

Conclusions: These changes to blood cell quantity and quality may be implicated in the development of Alzheimer's disease and contribute to the course of the illness.

Citing Articles

Functional Assessment of Cerebral Capillaries using Single Capillary Reporters in Ultrasound Localization Microscopy.

Lee S, Leconte A, Wu A, Kinugasa J, Poree J, Linninger A ArXiv. 2024; .

PMID: 39040644 PMC: 11261989.

Evaluation of cerebral microcirculation in a mouse model of systemic inflammation.

Zhang C, Jamshidi M, Delafontaine-Martel P, Linninger A, Lesage F Neurophotonics. 2024; 11(3):035003.

PMID: 39011517 PMC: 11249390. DOI: 10.1117/1.NPh.11.3.035003.

References

Zhang Q, Lan Y, He X, Luo C, Wang Q, Liang F . Allopurinol protects against ischemic insults in a mouse model of cortical microinfarction. Brain Res. 2015; 1622:361-7. DOI: 10.1016/j.brainres.2015.07.010. View

Hudetz A, Feher G, Kampine J . Heterogeneous autoregulation of cerebrocortical capillary flow: evidence for functional thoroughfare channels?. Microvasc Res. 1996; 51(1):131-6. DOI: 10.1006/mvre.1996.0015. View

Chen S, Bu X, Jin W, Shen L, Wang J, Zhuang Z . Altered peripheral profile of blood cells in Alzheimer disease: A hospital-based case-control study. Medicine (Baltimore). 2017; 96(21):e6843. PMC: 5457855. DOI: 10.1097/MD.0000000000006843. View

Bertsch K, Hagemann D, Hermes M, Walter C, Khan R, Naumann E . Resting cerebral blood flow, attention, and aging. Brain Res. 2009; 1267:77-88. DOI: 10.1016/j.brainres.2009.02.053. View

Kleinfeld D, Mitra P, Helmchen F, Denk W . Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex. Proc Natl Acad Sci U S A. 1998; 95(26):15741-6. PMC: 28114. DOI: 10.1073/pnas.95.26.15741. View

Mantegazza A, Clavica F, Obrist D . investigations of red blood cell phase separation in a complex microchannel network. Biomicrofluidics. 2020; 14(1):014101. PMC: 6941945. DOI: 10.1063/1.5127840. View

Salthouse T . The processing-speed theory of adult age differences in cognition. Psychol Rev. 1996; 103(3):403-28. DOI: 10.1037/0033-295x.103.3.403. View

El Amki M, Gluck C, Binder N, Middleham W, Wyss M, Weiss T . Neutrophils Obstructing Brain Capillaries Are a Major Cause of No-Reflow in Ischemic Stroke. Cell Rep. 2020; 33(2):108260. DOI: 10.1016/j.celrep.2020.108260. View

Maeda K, Mies G, Olah L, Hossmann K . Quantitative measurement of local cerebral blood flow in the anesthetized mouse using intraperitoneal [14C]iodoantipyrine injection and final arterial heart blood sampling. J Cereb Blood Flow Metab. 2000; 20(1):10-4. DOI: 10.1097/00004647-200001000-00003. View

10.

Summers P, Hartmann D, Hui E, Nie X, Deardorff R, McKinnon E . Functional deficits induced by cortical microinfarcts. J Cereb Blood Flow Metab. 2017; 37(11):3599-3614. PMC: 5669342. DOI: 10.1177/0271678X16685573. View

11.

Kalaria R . Cerebral vessels in ageing and Alzheimer's disease. Pharmacol Ther. 1996; 72(3):193-214. DOI: 10.1016/s0163-7258(96)00116-7. View

12.

Ji X, Ferreira T, Friedman B, Liu R, Liechty H, Bas E . Brain microvasculature has a common topology with local differences in geometry that match metabolic load. Neuron. 2021; 109(7):1168-1187.e13. PMC: 8525211. DOI: 10.1016/j.neuron.2021.02.006. View

13.

Wang M, Iliff J, Liao Y, Chen M, Shinseki M, Venkataraman A . Cognitive deficits and delayed neuronal loss in a mouse model of multiple microinfarcts. J Neurosci. 2012; 32(50):17948-60. PMC: 3541041. DOI: 10.1523/JNEUROSCI.1860-12.2012. View

14.

Nishimura N, Schaffer C, Friedman B, Lyden P, Kleinfeld D . Penetrating arterioles are a bottleneck in the perfusion of neocortex. Proc Natl Acad Sci U S A. 2006; 104(1):365-70. PMC: 1765467. DOI: 10.1073/pnas.0609551104. View

15.

Schmid F, Conti G, Jenny P, Weber B . The severity of microstrokes depends on local vascular topology and baseline perfusion. Elife. 2021; 10. PMC: 8421069. DOI: 10.7554/eLife.60208. View

16.

Blinder P, Tsai P, Kaufhold J, Knutsen P, Suhl H, Kleinfeld D . The cortical angiome: an interconnected vascular network with noncolumnar patterns of blood flow. Nat Neurosci. 2013; 16(7):889-97. PMC: 4141079. DOI: 10.1038/nn.3426. View

17.

Peyrounette M, Davit Y, Quintard M, Lorthois S . Multiscale modelling of blood flow in cerebral microcirculation: Details at capillary scale control accuracy at the level of the cortex. PLoS One. 2018; 13(1):e0189474. PMC: 5764267. DOI: 10.1371/journal.pone.0189474. View

18.

Silasi G, She J, Boyd J, Xue S, Murphy T . A mouse model of small-vessel disease that produces brain-wide-identified microocclusions and regionally selective neuronal injury. J Cereb Blood Flow Metab. 2015; 35(5):734-8. PMC: 4420872. DOI: 10.1038/jcbfm.2015.8. View

19.

Gertz K, Priller J, Kronenberg G, Fink K, Winter B, Schrock H . Physical activity improves long-term stroke outcome via endothelial nitric oxide synthase-dependent augmentation of neovascularization and cerebral blood flow. Circ Res. 2006; 99(10):1132-40. DOI: 10.1161/01.RES.0000250175.14861.77. View

20.

Gould I, Tsai P, Kleinfeld D, Linninger A . The capillary bed offers the largest hemodynamic resistance to the cortical blood supply. J Cereb Blood Flow Metab. 2016; 37(1):52-68. PMC: 5363755. DOI: 10.1177/0271678X16671146. View