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Demonstration of age-related blood-brain barrier disruption and cerebromicrovascular rarefaction in mice by longitudinal intravital two-photon microscopy and optical coherence tomography
Nyúl-Tóth Á, Tarantini S, DelFavero J, Yan F, Balasubramanian P, Yabluchanskiy A, Ahire C, Kiss T et al.. American journal of physiology. Heart and circulatory physiology, 2021-02-05
Topic: Brain proteins, microglia and lab models
Plain-language summary
Age-related blood-brain barrier (BBB) disruption and cerebromicrovascular rarefaction contribute importantly to the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Recent advances in geroscience research enable development of novel interventions to reverse age-related alterations of the cerebral microcirculation for prevention of VCID and AD. To facilitate this research, there is an urgent need for sensitive and easy-to-adapt imaging methods that enable longitudinal assessment of changes in BBB permeability and brain capillarization in aged mice and that could be used in vivo to evaluate treatment efficiency. To enable longitudinal assessment of changes in BBB permeability in aged mice equipped with a chronic cranial window, we adapted and optimized two different intravital two-photon imaging approaches. By assessing relative fluorescence changes over the baseline within a volume of brain tissue, after qualitative image subtraction of the brain microvasculature, we confirmed that, in 24-mo-old C57BL/6J mice, cumulative permeability of the microvessels to fluorescent tracers of different molecular masses (0.3 to 40 kDa) is significantly increased compared with that of 5-mo-old mice. Real-time recording of vessel cross-sections showed that apparent solute permeability of single microvessels is significantly increased in aged mice vs. young mice. Cortical capillary density, assessed both by intravital two-photon microscopy and optical coherence tomography was also decreased in aged mice vs. young mice. The presented methods have been optimized for longitudinal (over the period of 36 wk) in vivo assessment of cerebromicrovascular health in preclinical geroscience research. NEW & NOTEWORTHY Methods are presented for longitudinal detection of age-related increase in blood-brain barrier permeability and microvascular rarefaction in the mouse cerebral cortex by intravital two-photon microscopy and optical coherence tomography.
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APA 7th
Á, N.-T., Tarantini, S., DelFavero, J., Yan, F., Balasubramanian, P., Yabluchanskiy, A., et al. (2021). Demonstration of age-related blood-brain barrier disruption and cerebromicrovascular rarefaction in mice by longitudinal intravital two-photon microscopy and optical coherence tomography. American journal of physiology. Heart and circulatory physiology. https://doi.org/10.1152/ajpheart.00709.2020
Vancouver
Á N.-T, Tarantini S, DelFavero J, Yan F, Balasubramanian P, Yabluchanskiy A, et al. Demonstration of age-related blood-brain barrier disruption and cerebromicrovascular rarefaction in mice by longitudinal intravital two-photon microscopy and optical coherence tomography. American journal of physiology. Heart and circulatory physiology. 2021. doi:10.1152/ajpheart.00709.2020. PMID: 33543687.
BibTeX
@article{a2021-33543687,
author = {Á, Nyúl-Tóth and Tarantini, S. and DelFavero, J. and Yan, F. and Balasubramanian, P. and Yabluchanskiy, A. and Ahire, C. and Kiss, T. and others},
title = {{Demonstration of age-related blood-brain barrier disruption and cerebromicrovascular rarefaction in mice by longitudinal intravital two-photon microscopy and optical coherence tomography}},
journal = {American journal of physiology. Heart and circulatory physiology},
year = {2021},
doi = {10.1152/ajpheart.00709.2020},
pmid = {33543687},
url = {https://doi.org/10.1152/ajpheart.00709.2020}
}
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Key findings
- By assessing relative fluorescence changes over the baseline within a volume of brain tissue, after qualitative image subtraction of the brain microvasculature, we confirmed that, in 24-mo-old C57BL/6J mice, cumulative permeability of the microvessels to fluorescent tracers of different molecular masses (0.3 to 40 kDa) is significantly increased compared with that of 5-mo-old mice.
- Real-time recording of vessel cross-sections showed that apparent solute permeability of single microvessels is significantly increased in aged mice vs. young mice.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 55/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 32 of the 58 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (American journal of physiology. Heart and circulatory physiology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mice”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33543687) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 32 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 32 of the 58 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
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