Dilated Virchow-Robin spaces are a marker for arterial disease in multiple sclerosis

Ineichen, Benjamin Victor; Cananau, Carmen; Plattén, Michael; Ouellette, Russell; Moridi, Thomas; Frauenknecht, Katrin; Okar, Serhat V.; Kulcsár, Zsolt; Kockum, Ingrid; Piehl, Fredrik; Reich, Daniel S.; Granberg, Tobias

doi:10.1016/j.ebiom.2023.104631

Cited by 9 publications

(4 citation statements)

References 43 publications

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“…The examination of the processes involved in the development of EPVS via the RTIWH mechanism is indeed a novel approach; however, it serves to enlighten us of this innate wound healing mechanism in all individuals that is involved in brain injury and prepared to respond to injury at a moments' notice. Importantly, it became obvious during this review that the development of EPVS via RTIWH mechanisms there exists a bidirectional relationship between PVS and neuroinflammation as described by Owens et al [52] and there also exists a bidirectional relation between neuroinflammation and development of EPVS (Figures 10 and 15) [78]. The brain is exposed to many injurious stimuli over time and in multiple diseases and syndromes such as obesity, metabolic syndrome, and type 2 diabetes mellitus.…”

Section: Discussionmentioning

confidence: 79%

Brain Injury: Response to Injury Wound Healing Mechanisms and Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

Hayden¹

2023

Preprint

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Embryonic genetic mechanisms are present in the brain and ready to be placed into action upon cellular injury termed the response to injury wound healing (RTIWH) mechanism. When injured, regional brain endothelial cells initially undergo activation and dysfunction with initiation of hemostasis, inflammation (peripheral leukocytes and innate microglia and perivascular macrophage cells), proliferation (astrogliosis), remodeling, repair, and resolution phases if the injurious stimuli are removed. In conditions wherein the injurious stimuli are chronic as occurs in obesity, metabolic syndrome, and type 2 diabetes mellitus this process does not undergo resolution and there is persistent RTIWH with remodeling. Indeed, the brain is unique, in that it utilizes its neuroglia: the microglia cell along with peripheral inflammatory cells and its astroglia instead of peripheral scar-forming fibrocytes/fibroblasts. The brain undergoes astrogliosis to form a gliosis scar instead of a fibrosis scar to protect the surrounding neuropil from regional parenchymal injury. One of the unique and evolving remodeling changes in the brain is the development of enlarged perivascular spaces (EPVS), which is the focus of this brief review. EPVS are important since they serve as a biomarker for cerebral small vessel disease and also represent an impairment of the effluxing glymphatic system that is important for the clearance of metabolic waste from the interstitial fluid to the cerebrospinal fluid and disposal. Therefore, it is important to better understand how the RTIWH mechanism is involved in the development of EPVS that are closely associated with and important to the development of premature and age-related cerebrovascular and neurodegenerative diseases with impaired cognition.

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Section: Discussionmentioning

confidence: 79%

Brain Injury: Response to Injury Wound Healing Mechanisms and Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

Hayden¹

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The examination of the processes involved in the development of EPVSs via the RTIWH mechanism is indeed a novel approach; however, it serves to enlighten us of this innate wound-healing mechanism in all individuals that is involved in brain injury and prepared to respond to injury at a moment’s notice. Importantly, it became obvious during this review that, during the development of EPVSs via RTIWH mechanisms, there exists a bidirectional relationship between PVSs and neuroinflammation, as described by Owens et al [ 52 ], and there also exists a bidirectional relation between neuroinflammation and the development of EPVSs ( Figure 10 and Figure 15 ) [ 77 ].…”

Section: Discussionmentioning

confidence: 95%

Brain Injury: Response to Injury Wound-Healing Mechanisms and Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

Hayden

2023

Medicina

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Embryonic genetic mechanisms are present in the brain and ready to be placed into action upon cellular injury, termed the response to injury wound-healing (RTIWH) mechanism. When injured, regional brain endothelial cells initially undergo activation and dysfunction with initiation of hemostasis, inflammation (peripheral leukocytes, innate microglia, and perivascular macrophage cells), proliferation (astrogliosis), remodeling, repair, and resolution phases if the injurious stimuli are removed. In conditions wherein the injurious stimuli are chronic, as occurs in obesity, metabolic syndrome, and type 2 diabetes mellitus, this process does not undergo resolution and there is persistent RTIWH with remodeling. Indeed, the brain is unique, in that it utilizes its neuroglia: the microglia cell, along with peripheral inflammatory cells and its astroglia, instead of peripheral scar-forming fibrocytes/fibroblasts. The brain undergoes astrogliosis to form a gliosis scar instead of a fibrosis scar to protect the surrounding neuropil from regional parenchymal injury. One of the unique and evolving remodeling changes in the brain is the development of enlarged perivascular spaces (EPVSs), which is the focus of this brief review. EPVSs are important since they serve as a biomarker for cerebral small vessel disease and also represent an impairment of the effluxing glymphatic system that is important for the clearance of metabolic waste from the interstitial fluid to the cerebrospinal fluid, and disposal. Therefore, it is important to better understand how the RTIWH mechanism is involved in the development of EPVSs that are closely associated with and important to the development of premature and age-related cerebrovascular and neurodegenerative diseases with impaired cognition.

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“… 14 , 16 , 39 PVS enlargement may reflect CSF fluid stasis and reduced flow leading to overall deficits in glymphatic clearance 40 , 41 , 42 because PVS load segmentation depends on image (typically T2w) resolution and quality, 15 , 43 , 44 and only includes the visibly enlarged PVS surrounding periarteries in WM. 45 , 46 Our CSFF potentially overcomes these limitations by accounting for all parenchymal CSF water in PVS, including microscale PVS that traditional imaging might miss.…”

Section: Discussionmentioning

confidence: 99%

Parenchymal CSF fraction is a measure of brain glymphatic clearance and positively associated with amyloid beta deposition on PET

Zhou,

Nguyen,

Chiang

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONMapping of microscopic changes in the perivascular space (PVS) of the cerebral cortex, beyond magnetic resonance‐visible PVS in white matter, may enhance our ability to diagnose Alzheimer's disease (AD) early.METHODSWe used the cerebrospinal fluid (CSF) water fraction (CSFF), a magnetic resonance imaging–based biomarker, to characterize brain parenchymal CSF water, reflecting microscopic PVS in parenchyma. We measured CSFF and amyloid beta (Aβ) using 11C Pittsburgh compound B positron emission tomography to investigate their relationship at both the subject and voxel levels.RESULTSOur research has demonstrated a positive correlation between the parenchymal CSFF, a non‐invasive imaging biomarker indicative of parenchymal glymphatic clearance, and Aβ deposition, observed at both individual and voxel‐based assessments in the posterior cingulate cortex.DISCUSSIONThis study shows that an increased parenchymal CSFF is associated with Aβ deposition, suggesting that CSFF could serve as a biomarker for brain glymphatic clearance, which can be used to detect early fluid changes in PVS predisposing individuals to the development of AD.Highlights Cerebrospinal fluid fraction (CSFF) could be a biomarker of parenchymal perivascular space. CSFF is positively associated with amyloid beta (Aβ) deposition at subject level. CSFF in an Aβ+ region is higher than in an Aβ– region in the posterior cingulate cortex. Correspondence is found between Aβ deposition and glymphatic clearance deficits measured by CSFF.

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Dilated Virchow-Robin spaces are a marker for arterial disease in multiple sclerosis

Cited by 9 publications

References 43 publications

Brain Injury: Response to Injury Wound Healing Mechanisms and Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

Brain Injury: Response to Injury Wound Healing Mechanisms and Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

Brain Injury: Response to Injury Wound-Healing Mechanisms and Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

Parenchymal CSF fraction is a measure of brain glymphatic clearance and positively associated with amyloid beta deposition on PET

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