Cited by 301Neuroinflammation and Neurodegeneration MechanismsBarrier Structure and Function StudiesNeurological Disease Mechanisms and Treatments

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Microglia–blood vessel interactions: a double-edged sword in brain pathologies

Dudvarski Stankovic, Nevenka, Teodorczyk, Marcin, Ploen, Robert, Zipp, Frauke, Schmidt, Mirko H. H.·2016·Acta Neuropathologica

DOI 10.1007/s00401-015-1524-y

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Abstract

Microglia are long-living resident immune cells of the brain, which secure a stable chemical and physical microenvironment necessary for the proper functioning of the central nervous system (CNS). These highly dynamic cells continuously scan their environment for pathogens and possess the ability to react to damage-induced signals in order to protect the brain. Microglia, together with endothelial cells (ECs), pericytes and astrocytes, form the functional blood-brain barrier (BBB), a specialized endothelial structure that selectively separates the sensitive brain parenchyma from blood circulation. Microglia are in bidirectional and permanent communication with ECs and their perivascular localization enables them to survey the influx of blood-borne components into the CNS. Furthermore, they may stimulate the opening of the BBB, extravasation of leukocytes and angiogenesis. However, microglia functioning requires tight control as their dysregulation is implicated in the initiation and progression of numerous neurological diseases. Disruption of the BBB, changes in blood flow, introduction of pathogens in the sensitive CNS niche, insufficient nutrient supply, and abnormal secretion of cytokines or expression of endothelial receptors are reported to prime and attract microglia. Such reactive microglia have been reported to even escalate the damage of the brain parenchyma as is the case in ischemic injuries, brain tumors, multiple sclerosis, Alzheimer's and Parkinson's disease. In this review, we present the current state of the art of the causes and mechanisms of pathological interactions between microglia and blood vessels and explore the possibilities of targeting those dysfunctional interactions for the development of future therapeutics.

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See all 301

Authors: Dudvarski Stankovic, N., Teodorczyk, M., Ploen, R., Zipp, F., & Schmidt, M. H. H.
Affiliations: Johannes Gutenberg University Mainz (DE)
German Cancer Research Center (DE)
Corresponding author: Schmidt, Mirko H. H.
ORCID: Zipp, Frauke
Schmidt, Mirko H. H.
Venue: Acta Neuropathologica
Publisher: Springer Science and Business Media LLC
Published: 2015-12-28
Volume: 131
Issue: 3
Pages: 347-363
ISSN: 0001-6322 (ISSN-L)
1432-0533
DOI: 10.1007/s00401-015-1524-y
OpenAlex: W2216083821
Cited by: 301
References: 207
Citations by year: 2026: 12 · 2025: 28 · 2024: 35 · 2023: 29 · 2022: 39 · 2021: 45 · 2020: 33 · 2019: 14 · 2018: 24 · 2017: 36 · 2016: 6
FWCI: 1.76
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Acta Neuropathologica (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft (CRC1080 A3, CRC1080 B9, SCHM 2159/2-1)
Deutsches Krebsforschungszentrum (German Cancer Consortium (DKTK) grant)
German Academic Exchange Service (DAAD scholarship)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: microglia, blood-brain barrier, pericytes, astrocytes, reactive microglia, blood-brain barrier disruption, leukocyte transmigration, angiogenesis, ischemic brain injury, brain tumors, multiple sclerosis, Alzheimer's disease, Parkinson's disease, neuroinflammation, therapeutic targeting
MeSH terms: Animals, Blood-Brain Barrier, Brain, Brain Diseases, Humans, Microglia, Endothelial Cells

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Microglia–blood vessel interactions: a double-edged sword in brain pathologies

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