Mechanisms of Cerebral Microvascular Disease in Chronic Kidney Disease

Fisher, Mark

doi:10.1016/j.jstrokecerebrovasdis.2020.105404

Cited by 6 publications

(1 citation statement)

References 15 publications

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“…CMBs are defined as hypointense foci visible on T2*-weighted and susceptible-weighted MRI (SWI) sequences which are characterized histologically by the presence of hemosiderin around small vessels ( 13 ). As a manifestation of cerebral small vessel pathologies, CMBs have been demonstrated in increasing diseases, such as stroke ( 14 ), traumatic brain injury ( 15 ), and chronic kidney disease ( 16 ). However, the prevalence of CMBs in acromegaly has not been documented.…”

Section: Discussionmentioning

confidence: 99%

Presence of cerebral microbleeds is associated with cognitive decline in acromegaly

Xie

Zhou

Zhang³

et al. 2022

Front. Oncol.

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BackgroundCognitive decline in acromegaly has gained increasing attention. Cerebral microbleeds (CMBs) as radiographic markers for microvascular injury have been linked to various types of cognitive decline. However, the association between CMB formation and acromegaly has not yet been quantified. This study is designed to investigate the prevalence and the radiographic patterns of CMBs and the association between cognitive function and acromegaly-related CMBs in growth hormone (GH)-secreting pituitary adenoma, which is characterized by acromegaly. MethodsIn a cohort of 55 patients with GH-secreting pituitary adenoma (acromegaly) and 70 healthy control (HC) patients, we determined the presence of CMBs using a 3.0-T MRI scanner. The numbers, locations, and grades of CMBs were determined via susceptibility-weighted imaging (SWI) and the Microbleed Anatomical Rating Scale. Obstructive sleep apnea (OSA) was assessed using the criteria of the American Academy of Sleep Medicine (AASM) Scoring Manual Version 2.2. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance within 3 days of admission. The association between CMBs and cognitive function as well as clinical characteristics was explored.ResultsThe incidence of CMBs was 29.1%, whereas that of OSA was 65.5% in acromegaly. There was a statistically significant difference in the prevalence of CMBs between subjects with and without acromegaly (29.1% and 5.3%, respectively) (p < 0.01). The age of acromegaly patients with CMBs was much younger compared with HCs with CMBs. Compared with HCs, a significant cognitive decline and the occurrence of OSA were demonstrated in patients with acromegaly (p < 0.01). Binary logistic regression analysis adjusted for age, education, and body mass index (BMI) revealed that CMB was an independent risk factor for cognitive impairment in patients with acromegaly (OR = 3.19, 95% CI 1.51–6.76, p = 0.002). Furthermore, in the logistic regression models adjusted for age, BMI, diabetes, and hypertension, OSA was independently associated with the occurrence of CMBs in patients with acromegaly (OR = 13.34, 95% CI 3.09–57.51, p = 0.001).ConclusionsA significant increase of CMBs was demonstrated in patients with acromegaly, which may be a result of OSA in acromegaly. The present study indicated that increasing CMBs are responsible for cognitive decline in patients with acromegaly.

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Section: Discussionmentioning

confidence: 99%

Presence of cerebral microbleeds is associated with cognitive decline in acromegaly

Xie

Zhou

Zhang³

et al. 2022

Front. Oncol.

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Prevalence and Risk Factors of Silent Cerebral Microbleeds in Patients with Coronary Artery Disease

Yokoyama

Kanzaki

Watanabe

et al. 2022

Journal of Stroke and Cerebrovascular Diseases

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Nose-to-brain delivery of stem cells in stroke: the role of extracellular vesicles

Borlongan,

Lee,

D’Egidio

et al. 2024

Stem Cells Translational Medicine

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Stem cell transplantation offers a promising therapy that can be administered days, weeks, or months after a stroke. We recognize 2 major mitigating factors that remain unresolved in cell therapy for stroke, notably: (1) well-defined donor stem cells and (2) mechanism of action. To this end, we advance the use of ProtheraCytes, a population of non-adherent CD34+ cells derived from human peripheral blood and umbilical cord blood, which have been processed under good manufacturing practice, with testing completed in a phase 2 clinical trial in post-acute myocardial infarction (NCT02669810). We also reveal a novel mechanism whereby ProtheraCytes secrete growth factors and extracellular vesicles (EVs) that are associated with angiogenesis and vasculogenesis. Our recent data revealed that intranasal transplantation of ProtheraCytes at 3 days after experimentally induced stroke in adult rats reduced stroke-induced behavioral deficits and histological damage up to 28 days post-stroke. Moreover, we detected upregulation of human CD63+ EVs in the ischemic brains of stroke animals that were transplanted with ProtheraCytes, which correlated with increased levels of DCX-labeled neurogenesis and VEGFR1-associated angiogenesis and vasculogenesis, as well as reduced Iba1-marked inflammation. Altogether, these findings overcome key laboratory-to-clinic translational hurdles, namely the identification of well-characterized, clinical grade ProtheraCytes and the elucidation of a potential CD63+ EV-mediated regenerative mechanism of action. We envision that additional translational studies will guide the development of clinical trials for intranasal ProtheraCytes allografts in stroke patients, with CD63 serving as a critical biomarker.

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Mechanisms of Cerebral Microvascular Disease in Chronic Kidney Disease

Cited by 6 publications

References 15 publications

Presence of cerebral microbleeds is associated with cognitive decline in acromegaly

Presence of cerebral microbleeds is associated with cognitive decline in acromegaly

Prevalence and Risk Factors of Silent Cerebral Microbleeds in Patients with Coronary Artery Disease

Nose-to-brain delivery of stem cells in stroke: the role of extracellular vesicles

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