Astrocytic endfeet re-cover blood vessels after removal by laser ablation

Kubotera, Hideaki; Ikeshima-Kataoka, Hiroko; Hatashita, Yoshiki; Mascaro, Anna Letizia Allegra; Pavone, Francesco S.; Inoue, Takafumi

doi:10.1038/s41598-018-37419-4

Cited by 97 publications

(87 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition to microglial analysis, we examined the protective effects of moderate physical exercise on vessel coverage by astrocytes in animals with chronic cerebral hypoperfusion. These cells are part of the neurovascular unit and BBB, playing a key role in the structure of the BBB, in the communication with neurons, glutamate homeostasis [62], and also stimulating the release of vasoactive compounds in microcirculation.…”

Section: Discussionmentioning

confidence: 99%

Physical exercise promotes astrocyte coverage of microvessels in a model of chronic cerebral hypoperfusion

Leardini-Tristão

Andrade

García

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

Background: Brain circulation disorders such as chronic cerebral hypoperfusion have been associated with a decline in cognitive function during the development of dementia. Astrocytes together with microglia participate in the immune response in the CNS and make them potential sentinels in the brain parenchyma. In addition, astrocytes coverage integrity has been related to brain homeostasis. Currently, physical exercise has been proposed as an effective intervention to promote brain function improvement. However, the neuroprotective effects of early physical exercise on the astrocyte communication with the microcirculation and the microglial activation in a chronic cerebral hypoperfusion model are still unclear. The aim of this study was to investigate the impact of early intervention with physical exercise on cognition, brain microcirculatory, and inflammatory parameters in an experimental model of chronic cerebral hypoperfusion induced by permanent bilateral occlusion of the common carotid arteries (2VO). Methods: Wistar rats aged 12 weeks were randomly divided into four groups: Sham-sedentary group (Sham-Sed), Sham-exercised group (Sham-Ex), 2VO-sedentary group (2VO-Sed), and 2VO-exercised group (2VO-Ex). The early intervention with physical exercise started 3 days after 2VO or Sham surgery during 12 weeks. Then, the brain functional capillary density and endothelial-leukocyte interactions were evaluated by intravital microscopy; cognitive function was evaluated by open-field test; hippocampus postsynaptic density protein 95 and synaptophysin were evaluated by western blotting; astrocytic coverage of the capillaries, microglial activation, and structural capillary density were evaluated by immunohistochemistry.Results: Early moderate physical exercise was able to normalize functional capillary density and reduce leukocyte rolling in the brain of animals with chronic cerebral hypoperfusion. These effects were accompanied by restore synaptic protein and the improvement of cognitive function. In addition, early moderate exercise improves astrocytes coverage in blood vessels of the cerebral cortex and hippocampus, decreases microglial activation in the hippocampus, and improves structural capillaries in the hippocampus.(Continued on next page) (Continued from previous page)Conclusions: Microcirculatory and inflammatory changes in the brain appear to be involved in triggering a cognitive decline in animals with chronic cerebral ischemia. Therefore, early intervention with physical exercise may represent a preventive approach to neurodegeneration caused by chronic cerebral hypoperfusion.

show abstract

Section: Discussionmentioning

confidence: 99%

Physical exercise promotes astrocyte coverage of microvessels in a model of chronic cerebral hypoperfusion

Leardini-Tristão

Andrade

García

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…Transplantation of astrocytes into nonneural tissues of adult rats induces barrier properties in local ECs (Janzer and Raff, 1987), and several astrocyte-secreted proteins are sufficient to induce EC barrier properties in vitro and in vivo, including Sonic hedgehog, angiotensin, and basic fibroblast growth factor (Alvarez et al, 2011; Sobue et al, 1999; Wosik et al, 2007). However, barrier properties arise during development before astrogliogenesis takes place (Ben-Zvi et al, 2014; Daneman et al, 2010a; Sohet et al, 2015; Sauvageot and Stiles, 2002), delaying astrocytic contact with ECs does not affect barrier formation (Saunders et al, 2016), and laser ablation of astrocyte endfeet in adult mice does not induce BBB leakage (Kubotera et al, 2019). These data suggest that astrocytes are not necessary for BBB formation, but perhaps provide dynamic BBB regulation in response to specific stimuli.…”

Section: Bbb Formation and Regulationmentioning

confidence: 99%

The blood–brain barrier in health and disease: Important unanswered questions

Profaci

Munji

Pulido

et al. 2020

Journal of Experimental Medicine

477

358

View full text Add to dashboard Cite

The blood vessels vascularizing the central nervous system exhibit a series of distinct properties that tightly control the movement of ions, molecules, and cells between the blood and the parenchyma. This “blood–brain barrier” is initiated during angiogenesis via signals from the surrounding neural environment, and its integrity remains vital for homeostasis and neural protection throughout life. Blood–brain barrier dysfunction contributes to pathology in a range of neurological conditions including multiple sclerosis, stroke, and epilepsy, and has also been implicated in neurodegenerative diseases such as Alzheimer’s disease. This review will discuss current knowledge and key unanswered questions regarding the blood–brain barrier in health and disease.

show abstract

“…One study concluded that there were no changes to the BBB based on the absence of leakage of Evans Blue (960 Da when unbound and 65-70 kDa when bound to albumin) and dextran (4 kDa) after laser ablation of astrocytes or endfeet followed by 2-photon imaging (Kubotera et al, 2019). Yet cell death was only confirmed by lack of a fluorescent eGFP signal, which can occur as a result of photobleaching after which the still-alive cell is no longer visible.…”

Section: Astrocyte Loss In the Adult Brain Causes Bbb Damage Of Variamentioning

confidence: 99%

“…Alternatively, it is possible that ablation of a single astrocyte or single endfoot is not sufficient to induce BBB damage and that secreted factors by neighboring cells are sufficient to maintain barrier integrity. Integrity of tight junctions and other barrier properties were not assessed in this study (Kubotera et al, 2019).…”

Section: Astrocyte Loss In the Adult Brain Causes Bbb Damage Of Variamentioning

confidence: 99%

“…A role for astrocytes in maintaining the blood-brain barrier (BBB) in the adult healthy brain is widely assumed, but little direct experimental evidence supports this conclusion. In fact, several recent studies ablating astrocytes suggest that astrocytes are not required to maintain BBB integrity (Kubotera et al, 2019;Schreiner et al, 2015;Tsai et al, 2012). The conclusion that astrocytes are involved in BBB initiation and maintenance is based on early work that transplanted glial progenitor cells into the developing main body cavity and the anterior chamber of the eye, which both normally lack a BBB.…”

Section: Introduction (726)mentioning

confidence: 99%

See 1 more Smart Citation

Astrocytes are necessary for blood-brain barrier maintenance in the adult mouse brain

Heithoff

George

Phares

et al. 2020

Preprint

View full text Add to dashboard Cite

224/250 words)In the adult brain, multiple cell types are known to produce factors that regulate blood-brain barrier properties, including astrocytes. Yet several recent studies disputed a role for mature astrocytes at the blood-brain barrier. To determine if astrocytes contribute a non-redundant and necessary function in maintaining the adult blood-brain barrier, we used a mouse model of tamoxifen-inducible astrocyte ablation. In adult mice, tamoxifen induction caused sparse apoptotic astrocyte cell death within 2 hours. Indicative of BBB damage, leakage of the small molecule Cadaverine and the large plasma protein fibrinogen into the brain parenchyma indicative of BBB damage was detected as early as astrocyte ablation was present. Vessels within and close to regions of astrocyte loss had lower expression of the tight junction protein zonula occludens-1 while endothelial glucose transporter 1 expression was undisturbed.Cadaverine leakage persisted for several weeks suggesting a lack of barrier repair. This is consistent with the finding that ablated astrocytes were not replaced. Adjacent astrocytes responded with partial non-proliferative astrogliosis, characterized by morphological changes and delayed phosphorylation of STAT3, which restricted dye leakage to the brain and vessel surface areas lacking coverage by astrocytes one month after ablation. In conclusion, astrocytes are necessary to maintain blood-brain barrier integrity in the adult brain. Blood-brain barrier-regulating factors secreted by other cell types, such as pericytes, are not sufficient to compensate for astrocyte loss. Main Points (250 characters)Mature astrocytes are necessary for maintenance of endothelial tight junctions in the adult brain.Ablated astrocytes are not replaced by proliferation or process extension of neighboring astrocytes resulting in long-term blood-brain barrier damage.

show abstract

Astrocytic endfeet re-cover blood vessels after removal by laser ablation

Cited by 97 publications

References 43 publications

Physical exercise promotes astrocyte coverage of microvessels in a model of chronic cerebral hypoperfusion

Physical exercise promotes astrocyte coverage of microvessels in a model of chronic cerebral hypoperfusion

The blood–brain barrier in health and disease: Important unanswered questions

Astrocytes are necessary for blood-brain barrier maintenance in the adult mouse brain

Contact Info

Product

Resources

About