A Revised View on Growth and Remodeling in the Retinal Vasculature

Rust, Ruslan; Grönnert, Lisa; Doğançay, Berre; Schwab, Martin E.

doi:10.1038/s41598-019-40135-2

Cited by 53 publications

(55 citation statements)

References 23 publications

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“…Evans blue signal area in ischemic brain sections was quantified by thresholding at fivefold background signal intensity of the intact sensorimotor cortex (perfused with EB). Pericyte and tight junction coverage of blood vessels was calculated as previously described with an automated Fiji (ImageJ) script (Rust et al, 2019a(Rust et al, , 2020 and normalized to the intact cortex. Briefly, 4-6 random ROIs were selected.…”

Section: Fluorescence Microscopy and Quantificationmentioning

confidence: 99%

Characterization of the Blood Brain Barrier Disruption in the Photothrombotic Stroke Model

et al. 2020

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Blood brain barrier (BBB) damage is an important pathophysiological feature of ischemic stroke which significantly contributes to development of severe brain injury and therefore is an interesting target for therapeutic intervention. A popular permanent occlusion model to study long term recovery following stroke is the photothrombotic model, which so far has not been anatomically characterized for BBB leakage beyond the acute phase. Here, we observed enhanced BBB permeability over a time course of 3 weeks in peri-infarct and core regions of the ischemic cortex. Slight increases in BBB permeability could also be seen in the contralesional cortex, hippocampus and the cerebellum at different time points, regions where lesion-induced degeneration of pathways is prominent. Severe damage of tight and adherens junctions and loss of pericytes was observed within the peri-infarct region. Overall, the photothrombotic stroke model reproduces a variety of features observed in human stroke and thus, represents a suitable model to study BBB damage and therapeutic approaches interfering with this process.

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Section: Fluorescence Microscopy and Quantificationmentioning

confidence: 99%

Characterization of the Blood Brain Barrier Disruption in the Photothrombotic Stroke Model

et al. 2020

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“…etc. were measured at a sequential stage of development to obtain characteristics of the vascular network shape [10].…”

Section: Plos Onementioning

confidence: 99%

Remodeling mechanisms determine size distributions in developing retinal vasculature

et al. 2020

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The development of retinal blood vessels has extensively been used as a model to study vascular pattern formation. To date, various quantitative measurements, such as size distribution have been performed, but the relationship between pattern formation mechanisms and these measurements remains unclear. In the present study, we first focus on the islands (small regions subdivided by the capillary network). We quantitatively measured the island size distribution in the retinal vascular network and found that it tended to exhibit an exponential distribution. We were able to recapitulate this distribution pattern in a theoretical model by implementing the stochastic disappearance of vessel segments around arteries could reproduce the observed exponential distribution of islands. Second, we observed that the diameter distribution of the retinal artery segment obeyed a power law. We theoretically showed that an equal bifurcation branch pattern and Murray's law could reproduce this pattern. This study demonstrates the utility of examining size distribution for understanding the mechanisms of vascular pattern formation.

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“…analyzed after 3 wk for vascular function (53), cell survival, synaptic and neurotransmitter activity, and regenerative processes. A subset of Nogo-A −/− and WT animals underwent functional blood perfusion analysis with laser Doppler flowmetry (n = 4 per group).…”

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confidence: 99%

Nogo-A targeted therapy promotes vascular repair and functional recovery following stroke

Rust

Grönnert

Gantner

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Stroke is a major cause of serious disability due to the brain’s limited capacity to regenerate damaged tissue and neuronal circuits. After ischemic injury, a multiphasic degenerative and inflammatory response is coupled with severely restricted vascular and neuronal repair, resulting in permanent functional deficits. Although clinical evidence indicates that revascularization of the ischemic brain regions is crucial for functional recovery, no therapeutics that promote angiogenesis after cerebral stroke are currently available. Besides vascular growth factors, guidance molecules have been identified to regulate aspects of angiogenesis in the central nervous system (CNS) and may provide targets for therapeutic angiogenesis. In this study, we demonstrate that genetic deletion of the neurite outgrowth inhibitor Nogo-A or one of its corresponding receptors, S1PR2, improves vascular sprouting and repair and reduces neurological deficits after cerebral ischemia in mice. These findings were reproduced in a therapeutic approach using intrathecal anti–Nogo-A antibodies; such a therapy is currently in clinical testing for spinal cord injury. These results provide a basis for a therapeutic blockage of inhibitory guidance molecules to improve vascular and neural repair after ischemic CNS injuries.

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A Revised View on Growth and Remodeling in the Retinal Vasculature

Cited by 53 publications

References 23 publications

Characterization of the Blood Brain Barrier Disruption in the Photothrombotic Stroke Model

Characterization of the Blood Brain Barrier Disruption in the Photothrombotic Stroke Model

Remodeling mechanisms determine size distributions in developing retinal vasculature

Nogo-A targeted therapy promotes vascular repair and functional recovery following stroke

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