Astrocyte dysfunction and neurovascular impairment in neurological disorders: Correlation or causation?

McConnell, Heather L.; Li, Zhenzhou; Woltjer, Randall L.; Mishra, Anusha

doi:10.1016/j.neuint.2019.04.005

Cited by 51 publications

(43 citation statements)

References 253 publications

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“…Indeed, our microarray data also suggest that astrocytes adopt a more reactive phenotype, which may also contribute to regulating the permeability of the BBB, either independently or in concert with microglia. Astrocytes, BBB integrity, and blood flow regulation are all closely linked, and astrocyte reactivity may be a key component in both acute and chronic brain diseases associated with altered BBB permeability 52 . Altered CLDN5 expression also regulates BBB integrity, where a decrease in CLDN5 increases BBB leakage.…”

Section: Discussionmentioning

confidence: 99%

Dual microglia effects on blood brain barrier permeability induced by systemic inflammation

et al. 2019

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Microglia survey brain parenchyma, responding to injury and infections. Microglia also respond to systemic disease, but the role of blood–brain barrier (BBB) integrity in this process remains unclear. Using simultaneous in vivo imaging, we demonstrated that systemic inflammation induces CCR5-dependent migration of brain resident microglia to the cerebral vasculature. Vessel-associated microglia initially maintain BBB integrity via expression of the tight-junction protein Claudin-5 and make physical contact with endothelial cells. During sustained inflammation, microglia phagocytose astrocytic end-feet and impair BBB function. Our results show microglia play a dual role in maintaining BBB integrity with implications for elucidating how systemic immune-activation impacts neural functions.

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Section: Discussionmentioning

confidence: 99%

Dual microglia effects on blood brain barrier permeability induced by systemic inflammation

et al. 2019

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“…In particular, reactive astrocytes are thought to be less efficient in mediating neurovascular coupling. Astrocytes dysregulation of NO production and downregulation of K+ channels have been described in AD model: the reduction of NO may hinder the vasodilation of capillaries, producing hypoperfusion and hypoxia, while deficiency of K+ channel could hamper K‐dependent Ca+ release, an important signaling pathway of NVU (McConnell, Li, Woltjer, & Mishra, 2019). Furthermore, reactive astrocytes could have lost, at least in part, their supporting role on BBB; the end feet layer around endothelium appears disorganized and discontinuous in AD, and it could compromise BBB structural and functional homeostasis (Zlokovic, 2008).…”

Section: Evidence and Mechanisms Of Nvu Alteration In Admentioning

confidence: 99%

Locus Coeruleus and neurovascular unit: From its role in physiology to its potential role in Alzheimer’s disease pathogenesis

Giorgi

Galgani²,

Puglisi-Allegra

et al. 2020

J of Neuroscience Research

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Locus coeruleus (LC) is the main noradrenergic (NA) nucleus of the central nervous system. LC degenerates early during Alzheimer's disease (AD) and NA loss might concur to AD pathogenesis. Aside from neurons, LC terminals provide dense innervation of brain intraparenchymal arterioles/capillaries, and NA modulates astrocyte functions. The term neurovascular unit (NVU) defines the strict anatomical/functional interaction occurring between neurons, glial cells, and brain vessels. NVU plays a fundamental role in coupling the energy demand of activated brain regions with regional cerebral blood flow, it includes the blood-brain barrier (BBB), plays an active role in neuroinflammation, and participates also to the glymphatic system. NVU alteration is involved in AD pathophysiology through several mechanisms, mainly related to a relative oligoemia in activated brain regions and impairment of structural and functional BBB integrity, which contributes also to the intracerebral accumulation of insoluble amyloid. We review the existing data on the morphological features of LC-NA innervation of the NVU, as well as its contribution to neurovascular coupling and BBB proper functioning. After introducing the main experimental data linking LC with AD, which have repeatedly shown a key role of neuroinflammation and increased amyloid plaque formation, we discuss the potential mechanisms by which the loss of NVU modulation by LC might contribute to AD pathogenesis. Surprisingly, thus far not so many studies have tested directly these mechanisms in models of AD in which LC has been lesioned experimentally. Clarifying the interaction of LC with NVU in AD pathogenesis may disclose potential therapeutic targets for AD.

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“…Following stroke, profound functional changes occur at the level of astrocytes, which significantly affects neurovascular coupling. At the cellular level, post-stroke astrogliosis is noticeable around brain vessels (McConnell et al, 2019). At the molecular level, intracellular factors in astrocytes affect their ability to respond to neurometabolic needs.…”

Section: Effects Of Stroke On Astrocyte Functionmentioning

confidence: 99%

“…-Angiogenic response provides a scaffold for neuronal regeneration, mediated by neural precursor cells. Marti et al, 2000;Attwell et al, 2010;Arimura et al, 2012;Fernandez-Klett et al, 2013;Hall et al, 2014;O'Donnell, 2014;Hoffmann et al, 2015;Reeson et al, 2015;Howarth et al, 2017;Cai et al, 2018;Rovegno and Saez, 2018;McConnell et al, 2019;Tornabene et al, 2019. Hemorrhagic stroke -VEGF and its receptors upregulated persistently.…”

Section: Functional Nvu Remodelingmentioning

confidence: 99%

Structural and Functional Remodeling of the Brain Vasculature Following Stroke

2020

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Astrocyte dysfunction and neurovascular impairment in neurological disorders: Correlation or causation?

Cited by 51 publications

References 253 publications

Dual microglia effects on blood brain barrier permeability induced by systemic inflammation

Dual microglia effects on blood brain barrier permeability induced by systemic inflammation

Locus Coeruleus and neurovascular unit: From its role in physiology to its potential role in Alzheimer’s disease pathogenesis

Structural and Functional Remodeling of the Brain Vasculature Following Stroke

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