2022
DOI: 10.1038/s41467-022-29475-2
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Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age

Abstract: Astrocytes extend endfeet that enwrap the vasculature, and disruptions to this association which may occur in disease coincide with breaches in blood-brain barrier (BBB) integrity. Here we investigate if focal ablation of astrocytes is sufficient to disrupt the BBB in mice. Targeted two-photon chemical apoptotic ablation of astrocytes induced a plasticity response whereby surrounding astrocytes extended processes to cover vascular vacancies. In young animals, replacement processes occur in advance of endfoot r… Show more

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Cited by 47 publications
(25 citation statements)
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“…Our results showed that amyloid aggregation but not the traumatic injury induced FMNL2 expression, suggesting that FMNL2-regulated astroglial endfeet remodeling could be preferentially related to AD pathophysiology. A recent study demonstrating that selective focal ablation of astroglia endfeet around the blood vessels does not cause blood–brain-barrier disruption and gliovascular contacts are efficiently replaced [ 62 ] supports our findings.…”
Section: Discussionsupporting
confidence: 90%
“…Our results showed that amyloid aggregation but not the traumatic injury induced FMNL2 expression, suggesting that FMNL2-regulated astroglial endfeet remodeling could be preferentially related to AD pathophysiology. A recent study demonstrating that selective focal ablation of astroglia endfeet around the blood vessels does not cause blood–brain-barrier disruption and gliovascular contacts are efficiently replaced [ 62 ] supports our findings.…”
Section: Discussionsupporting
confidence: 90%
“…Dysregulated reactive astrocytes, on the other hand, destroy the structure of BBB by producing factors to decrease the permeability of BBB. Furthermore, the physical structure of BBB, which is composed of astrocyte end-feet and endothelial cells, is destroyed in reactive astrocytes (Mills et al, 2022). Glial cells-induced neuroinflammation exacerbates BBB damage and reduces its integrity.…”
Section: The Basic Role Of Astrocytes In Neurodegenerationmentioning
confidence: 99%
“…Additionally, Kubotera et al [ 41 ] observed that after laser ablation astrocytes restore the endfoot coverage of microvessels in-vivo. (Mills and coworkers call this tendency to re-cover blood vessels after disruptions endfoot plasticity [ 42 ].) On the other end, the effective gap area fraction is reduced, if inter-endfoot gap junctions (2–3 nm [ 14 ]) are found to be present in-vivo with significant density (neglected in this work).…”
Section: Discussionmentioning
confidence: 99%