Pericytes: Intrinsic Transportation Engineers of the CNS Microcirculation

Overview

Journal Front Physiol

Date 2021 Sep 9

PMID 34497540

Citations 9

Authors

Ahmed M Eltanahy

Yara A Koluib

Albert Gonzales

Affiliations

Soon will be listed here.

Abstract

Pericytes in the brain are candidate regulators of microcirculatory blood flow because they are strategically positioned along the microvasculature, contain contractile proteins, respond rapidly to neuronal activation, and synchronize microvascular dynamics and neurovascular coupling within the capillary network. Analyses of mice with defects in pericyte generation demonstrate that pericytes are necessary for the formation of the blood-brain barrier, development of the glymphatic system, immune homeostasis, and white matter function. The development, identity, specialization, and progeny of different subtypes of pericytes, however, remain unclear. Pericytes perform brain-wide 'transportation engineering' functions in the capillary network, instructing, integrating, and coordinating signals within the cellular communicome in the neurovascular unit to efficiently distribute oxygen and nutrients ('goods and services') throughout the microvasculature ('transportation grid'). In this review, we identify emerging challenges in pericyte biology and shed light on potential pericyte-targeted therapeutic strategies.

Citing Articles

The Crucial Role of the Blood-Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications.

Kim S, Jung U, Kim S J Clin Med. 2025; 14(2).

PMID: 39860392 PMC: 11765772. DOI: 10.3390/jcm14020386.

Progress of the study of pericytes and their potential research value in adenomyosis.

Zhang C, Shi J, Dai Y, Li X, Leng J Sci Prog. 2024; 107(2):368504241257126.

PMID: 38863331 PMC: 11179483. DOI: 10.1177/00368504241257126.

Leveraging the glymphatic and meningeal lymphatic systems as therapeutic strategies in Alzheimer's disease: an updated overview of nonpharmacological therapies.

Formolo D, Yu J, Lin K, Tsang H, Ou H, Kranz G Mol Neurodegener. 2023; 18(1):26.

PMID: 37081555 PMC: 10116684. DOI: 10.1186/s13024-023-00618-3.

Potential of Lipid-Based Nanocarriers against Two Major Barriers to Drug Delivery-Skin and Blood-Brain Barrier.

Khan M, Mohapatra S, Gupta V, Ali A, Naseef P, Kurunian M Membranes (Basel). 2023; 13(3).

PMID: 36984730 PMC: 10058721. DOI: 10.3390/membranes13030343.

The post-arteriole transitional zone: a specialized capillary region that regulates blood flow within the CNS microvasculature.

Mughal A, Nelson M, Hill-Eubanks D J Physiol. 2023; 601(5):889-901.

PMID: 36751860 PMC: 9992301. DOI: 10.1113/JP282246.

References

Risson E, Nobre A, Maguer-Satta V, Aguirre-Ghiso J . The current paradigm and challenges ahead for the dormancy of disseminated tumor cells. Nat Cancer. 2021; 1(7):672-680. PMC: 7929485. DOI: 10.1038/s43018-020-0088-5. View

Stoeltzing O, Meric-Bernstam F, Ellis L . Intracellular signaling in tumor and endothelial cells: The expected and, yet again, the unexpected. Cancer Cell. 2006; 10(2):89-91. DOI: 10.1016/j.ccr.2006.07.013. View

Dalkara T . Pericytes: A Novel Target to Improve Success of Recanalization Therapies. Stroke. 2019; 50(10):2985-2991. DOI: 10.1161/STROKEAHA.118.023590. View

Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T . Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med. 2009; 15(9):1031-7. DOI: 10.1038/nm.2022. View

Ostergaard L . SARS CoV-2 related microvascular damage and symptoms during and after COVID-19: Consequences of capillary transit-time changes, tissue hypoxia and inflammation. Physiol Rep. 2021; 9(3):e14726. PMC: 7849453. DOI: 10.14814/phy2.14726. View

Kang T, Bocci F, Jolly M, Levine H, Onuchic J, Levchenko A . Pericytes enable effective angiogenesis in the presence of proinflammatory signals. Proc Natl Acad Sci U S A. 2019; 116(47):23551-23561. PMC: 6876202. DOI: 10.1073/pnas.1913373116. View

Wimmer R, Leopoldi A, Aichinger M, Kerjaschki D, Penninger J . Generation of blood vessel organoids from human pluripotent stem cells. Nat Protoc. 2019; 14(11):3082-3100. DOI: 10.1038/s41596-019-0213-z. View

Sugimoto K, Chung D, Bohm M, Fischer P, Takizawa T, Aykan S . Peri-Infarct Hot-Zones Have Higher Susceptibility to Optogenetic Functional Activation-Induced Spreading Depolarizations. Stroke. 2020; 51(8):2526-2535. PMC: 7387208. DOI: 10.1161/STROKEAHA.120.029618. View

Cleuren A, van der Ent M, Jiang H, Hunker K, Yee A, Siemieniak D . The in vivo endothelial cell translatome is highly heterogeneous across vascular beds. Proc Natl Acad Sci U S A. 2019; 116(47):23618-23624. PMC: 6876253. DOI: 10.1073/pnas.1912409116. View

10.

Dreier J . The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat Med. 2011; 17(4):439-47. DOI: 10.1038/nm.2333. View

11.

Soto I, Grabowska W, Onos K, Graham L, Jackson H, Simeone S . Meox2 haploinsufficiency increases neuronal cell loss in a mouse model of Alzheimer's disease. Neurobiol Aging. 2016; 42:50-60. PMC: 4878023. DOI: 10.1016/j.neurobiolaging.2016.02.025. View

12.

Valdor R, Garcia-Bernal D, Riquelme D, Martinez C, Moraleda J, Cuervo A . Glioblastoma ablates pericytes antitumor immune function through aberrant up-regulation of chaperone-mediated autophagy. Proc Natl Acad Sci U S A. 2019; 116(41):20655-20665. PMC: 6789971. DOI: 10.1073/pnas.1903542116. View

13.

Bahr-Hosseini M, Bikson M . Neurovascular-modulation: A review of primary vascular responses to transcranial electrical stimulation as a mechanism of action. Brain Stimul. 2021; 14(4):837-847. DOI: 10.1016/j.brs.2021.04.015. View

14.

Shen H . Core Concept: Can deep brain stimulation find success beyond Parkinson's disease?. Proc Natl Acad Sci U S A. 2019; 116(11):4764-4766. PMC: 6421452. DOI: 10.1073/pnas.1900442116. View

15.

Wang S, Cao C, Chen Z, Bankaitis V, Tzima E, Sheibani N . Pericytes regulate vascular basement membrane remodeling and govern neutrophil extravasation during inflammation. PLoS One. 2012; 7(9):e45499. PMC: 3448630. DOI: 10.1371/journal.pone.0045499. View

16.

Chen L, Li X, Chen M, Feng Y, Xiong C . The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020; 116(6):1097-1100. PMC: 7184507. DOI: 10.1093/cvr/cvaa078. View

17.

Zhang S, Wan Z, Kamm R . Vascularized organoids on a chip: strategies for engineering organoids with functional vasculature. Lab Chip. 2021; 21(3):473-488. PMC: 8283929. DOI: 10.1039/d0lc01186j. View

18.

Hablitz L, Pla V, Giannetto M, Vinitsky H, Staeger F, Metcalfe T . Circadian control of brain glymphatic and lymphatic fluid flow. Nat Commun. 2020; 11(1):4411. PMC: 7468152. DOI: 10.1038/s41467-020-18115-2. View

19.

Wierenga C, Clark L, Dev S, Shin D, Jurick S, Rissman R . Interaction of age and APOE genotype on cerebral blood flow at rest. J Alzheimers Dis. 2013; 34(4):921-35. PMC: 4124882. DOI: 10.3233/JAD-121897. View

20.

Toussay X, Basu K, Lacoste B, Hamel E . Locus coeruleus stimulation recruits a broad cortical neuronal network and increases cortical perfusion. J Neurosci. 2013; 33(8):3390-401. PMC: 6619527. DOI: 10.1523/JNEUROSCI.3346-12.2013. View