Imaging subtle leaks in the blood–brain barrier in the aging human brain: potential pitfalls, challenges, and possible solutions

Montagne, Axel; Barnes, Samuel; Nation, Daniel A.; Kisler, Kassandra; Toga, Arthur W.; Zloković, Berislav V.

doi:10.1007/s11357-022-00571-x

Cited by 24 publications

(31 citation statements)

References 86 publications

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“…diabetes mellitus [127], psychostimulant abuse [128], traumatic brain injury [61], chronic stress [129] DCE MRI [130][131][132][133][134][135][136][137], water-exchange MRI [28,84,138], PET [139][140][141], intravital microscopy of dextran leakage [129,142] Upregulation of cellular adhesion molecules…”

Section: In Vivo Imaging Techniques Of the Bbbmentioning

confidence: 99%

In vivo methods for imaging blood–brain barrier function and dysfunction

Harris

Asselin

Hinz

et al. 2022

Eur J Nucl Med Mol Imaging

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The blood–brain barrier (BBB) is the interface between the central nervous system and systemic circulation. It tightly regulates what enters and is removed from the brain parenchyma and is fundamental in maintaining brain homeostasis. Increasingly, the BBB is recognised as having a significant role in numerous neurological disorders, ranging from acute disorders (traumatic brain injury, stroke, seizures) to chronic neurodegeneration (Alzheimer’s disease, vascular dementia, small vessel disease). Numerous approaches have been developed to study the BBB in vitro, in vivo, and ex vivo. The complex multicellular structure and effects of disease are difficult to recreate accurately in vitro, and functional aspects of the BBB cannot be easily studied ex vivo. As such, the value of in vivo methods to study the intact BBB cannot be overstated. This review discusses the structure and function of the BBB and how these are affected in diseases. It then discusses in depth several established and novel methods for imaging the BBB in vivo, with a focus on MRI, nuclear imaging, and high-resolution intravital fluorescence microscopy.

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Section: In Vivo Imaging Techniques Of the Bbbmentioning

confidence: 99%

In vivo methods for imaging blood–brain barrier function and dysfunction

Harris

Asselin

Hinz

et al. 2022

Eur J Nucl Med Mol Imaging

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“…We acknowledge the importance to the vascular contributions to cognitive function ( Custodero et al, 2022 ; Kiss et al, 2022 ; Montagne et al, 2022 ). Acupuncture was found can alleviate cognitive function in Vascular dementia (VD), but the underlying mechanisms are still unclear ( Cao et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Exploration of acupuncture therapy in the treatment of mild cognitive impairment based on the brain-gut axis theory

Jin

Zhu

2022

Front. Hum. Neurosci.

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BackgroundMild cognitive impairment (MCI) is an intermediary state between normal aging and dementia. Early intervention for MCI may be a key opportunity in managing dementia. Recent studies have demonstrated the alterations in the gut microbial communities associated with MCI. This study aims to evaluate if acupuncture can improve cognitive function in subjects with MCI and explore the possible mechanism of acupuncture by better defining the interactions of gut microbiota.MethodsA randomized assessor-blind controlled study is proposed. A total of 62 subjects will be recruited and randomly allocated into two groups in a 1:1 ratio: the treatment and control groups. Participants in the treatment group will receive active acupuncture and exercise/cognitive training (conventional treatment). The control group will receive sham acupuncture and exercise/cognitive training. Each participant will receive active or sham acupuncture for 12 weeks. The primary outcome will be the Montreal Cognitive Assessment (MoCA) score and intestinal flora. Secondary outcomes will include mini-mental state examination (MMSE) and activity of daily living (ADL) scores. Various scales will be collected at baseline, during the treatment (weeks 4 and 8), week 12, and months 4 and 6 after the intervention. Feces will be collected before and after the treatment based on 16S rRNA gene sequencing technology for each participant to characterize the intestinal flora. Adverse events will be recorded by monthly follow-up.ResultsThe trial is expected to show that cognitive function can be improved by acupuncture and produce reliable clinical outcomes in MCI patients. It will also provide preliminary data on the possible mechanism based on the changes in the intestinal flora. Collected data will be used to support future large-scale fundamental studies.ConclusionAcupuncture is an effective method to improve cognitive function for MCI. This study will provide data on the relationship between gut microbiota and the effectiveness of acupuncture in patients with MCI from a new angle.Clinical trial registration[www.ClinicalTrials.gov], identifier [MR-33-22-002376].

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“…The BBB is a functional part of the NVU and is critical for the protection of neurons, maintenance of homeostasis, and the integrity of the brain itself ( 19 , 237 , 238 ). BBB dysfunction is one of the hallmarks of the aging brain, in both humans and animal models ( 19 , 33 , 34 , 239 – 241 ). The BBB comprises brain capillary endothelial cells with support from pericytes embedded in the basement membrane and astrocytes.…”

Section: Role Of Gh/igf-1 In Regulation Of Cerebrovascular Functionmentioning

confidence: 99%

Cell non-autonomous regulation of cerebrovascular aging processes by the somatotropic axis

et al. 2023

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Age-related cerebrovascular pathologies, ranging from cerebromicrovascular functional and structural alterations to large vessel atherosclerosis, promote the genesis of vascular cognitive impairment and dementia (VCID) and exacerbate Alzheimer’s disease. Recent advances in geroscience, including results from studies on heterochronic parabiosis models, reinforce the hypothesis that cell non-autonomous mechanisms play a key role in regulating cerebrovascular aging processes. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) exert multifaceted vasoprotective effects and production of both hormones is significantly reduced in aging. This brief overview focuses on the role of age-related GH/IGF-1 deficiency in the development of cerebrovascular pathologies and VCID. It explores the mechanistic links among alterations in the somatotropic axis, specific macrovascular and microvascular pathologies (including capillary rarefaction, microhemorrhages, impaired endothelial regulation of cerebral blood flow, disruption of the blood brain barrier, decreased neurovascular coupling, and atherogenesis) and cognitive impairment. Improved understanding of cell non-autonomous mechanisms of vascular aging is crucial to identify targets for intervention to promote cerebrovascular and brain health in older adults.

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Imaging subtle leaks in the blood–brain barrier in the aging human brain: potential pitfalls, challenges, and possible solutions

Cited by 24 publications

References 86 publications

In vivo methods for imaging blood–brain barrier function and dysfunction

In vivo methods for imaging blood–brain barrier function and dysfunction

Exploration of acupuncture therapy in the treatment of mild cognitive impairment based on the brain-gut axis theory

Cell non-autonomous regulation of cerebrovascular aging processes by the somatotropic axis

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