Structure and function of the perivascular fluid compartment and vertebral venous plexus: Illumining a novel theory on mechanisms underlying the pathogenesis of Alzheimer's, cerebral small vessel, and neurodegenerative diseases

Ghali, Michael George Zaki; Marchenko, Vitaliy; Yaşargil, M. Gazi; Ghali, George Zaki

doi:10.1016/j.nbd.2020.105022

Cited by 10 publications

(8 citation statements)

References 240 publications

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“…However, the PVS system of fluid drainage and waste clearance is not fully understood. PVS burden has been associated with brain atrophy with aging, inflammation leading to increased oxygen consumption, cerebrovascular reactivity and hypoperfusion, and disruption of the blood-brain barrier (Joutel et al, 2010;Aribisala et al, 2014;Adams et al, 2015;Rost et al, 2018;Ghali et al, 2020). Recent findings suggest that the PVS system may be an immunological hotspot, which is the site of antigen presentation and tissue-resident memory T-cell reactivation (Smolders et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

Song

et al. 2020

Front. Aging Neurosci.

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Background: Excessive aggregation of α-synuclein is the key pathophysiological feature of Parkinson's disease (PD). Rapid eye movement sleep behavior disorder (RBD) is also associated with synucleinopathies and considered as a powerful predictor of PD. Growing evidence suggests the diminished clearance of α-synuclein may be partly attributable to poor interstitial fluid drainage, which can be reflected by magnetic resonance imaging (MRI)-visible enlarged perivascular space (EPVS). However, the effect of MRI-visible EPVS on iRBD and PD, and their correlation with clinical characteristics remain unclear. Objective: To evaluate the clinical and neuroimaging significance of MRI-visible EPVS in iRBD and PD patients. Methods: We enrolled 33 iRBD patients, 82 PD (with and without RBD) patients, and 35 healthy controls (HCs), who underwent clinical evaluation and 3.0 Tesla MRI. Two neurologists assessed MRI-visible EPVS in centrum semiovale (CSO), basal ganglia (BG), substantia nigra (SN), and brainstem (BS). Independent risk factors for iRBD and PD were investigated using multivariable logistic regression analysis. Spearman analysis was used to test the correlation of MRI-visible EPVS with clinical characteristics of patients. Results: iRBD patients had significantly higher EPVS burdens (CSO, BG, SN, and BS) than PD patients. Higher CSO-EPVS and BS-EPVS burdens were independent risk factors for iRBD. Furthermore, higher CSO-EPVS and SN-EPVS burdens were positively correlated with the severity of clinical symptom in iRBD patients, and higher BG-EPVS burden was positively correlated with the severity of cognitive impairment in PD patients. Conclusion: iRBD and PD patients have different MRI-visible EPVS burdens, which may be related with a compensatory mechanism in glymphatic system. Lower MRI-visible EPVS burden in PD patients may be a manifestation of severe brain waste drainage dysfunction. These findings shed light on the pathophysiologic relationship between iRBD and PD with respect to neuroimaging marker of PD.

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Section: Discussionmentioning

confidence: 99%

Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

Song

et al. 2020

Front. Aging Neurosci.

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“…Since Aβ in the ISF of the brain can be removed from the brain through the glymphatic perivenous drainage pathway and/or IPAD pathway [ 34 ], perivascular Aβ deposition is detected in both the cortex and hippocampus. We found that the distribution of Aβ deposits changed from amyloid plaques to Aβ deposits around blood vessels after treatment with EK100 and antrodin C ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

EK100 and Antrodin C Improve Brain Amyloid Pathology in APP/PS1 Transgenic Mice by Promoting Microglial and Perivascular Clearance Pathways

Tsay

Liu

Kuo

et al. 2021

IJMS

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Alzheimer’s disease (AD) is characterized by the deposition of β-amyloid peptide (Aβ). There are currently no drugs that can successfully treat this disease. This study first explored the anti-inflammatory activity of seven components isolated from Antrodia cinnamonmea in BV2 cells and selected EK100 and antrodin C for in vivo research. APPswe/PS1dE9 mice were treated with EK100 and antrodin C for one month to evaluate the effect of these reagents on AD-like pathology by nesting behavior, immunohistochemistry, and immunoblotting. Ergosterol and ibuprofen were used as control. EK100 and antrodin C improved the nesting behavior of mice, reduced the number and burden of amyloid plaques, reduced the activation of glial cells, and promoted the perivascular deposition of Aβ in the brain of mice. EK100 and antrodin C are significantly different in activating astrocytes, regulating microglia morphology, and promoting plaque-associated microglia to express oxidative enzymes. In contrast, the effects of ibuprofen and ergosterol are relatively small. In addition, EK100 significantly improved hippocampal neurogenesis in APPswe/PS1dE9 mice. Our data indicate that EK100 and antrodin C reduce the pathology of AD by reducing amyloid deposits and promoting nesting behavior in APPswe/PS1dE9 mice through microglia and perivascular clearance, indicating that EK100 and antrodin C have the potential to be used in AD treatment.

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“…전체적으로 EPVS는 대뇌피질보다는 뇌백질에 발생하기 쉬운데, 뇌백질의 경우 피질에 비하여 세포 밀도가 낮고 피질의 경우 본질적으로 치밀한 구조가 PVS의 확장을 억제하기 때문으로 이해하고 있다( 37 ). CSF 공간에 비정상적인 독소 침착 등에 의해 염증 반응이 일어나게 되는 경우 이는 순차적으로 extracellular matrix의 파괴와 BBB의 투과성을 증가시키게 되며, 이는 PVS의 확장과 대뇌 fluid dynamic의 장애를 초래하게 된다( 49 50 ).…”

Section: Pvs의 영상해부학및 병리적 영상 소견unclassified

An Enlarged Perivascular Space: Clinical Relevance and the Role of Imaging in Aging and Neurologic Disorders

Yim

Moon

2022

J Korean Soc Radiol

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혈관주위공간(perivascular space; 이하 PVS)는 뇌 실질을 관통하는 세동맥 둘러싸고 있는 공간으로, 최근에는 별아교세포의 종족(astrocyte endfoot)에 의해 가장 바깥쪽이 경계지워지는, 체액, 세포, 결합조직으로 구성된 혈관벽내, 혈관벽 주위의 구획을 모두 아우르는 개념으로 이해하고 있다. 정상적으로는 현미경적 해부학 구조물이지만 이 구조물이 늘어나게 되면 MRI T1 혹은 T2 이미지에서 확인할 수 있게 된다. PVS의 명확한 실체나 임상적인 의의에 대해서는 아직 분명치 않은 부분이 많이 있지만 PVS의 확장(enlarged PVS; 이하 EPVS)은 다양한 퇴행성 뇌질환 뿐만 아니라 뇌출혈 및 외상성 뇌손상, 당뇨성 신질환 같은 다양한 질병과의 연관성이 있다는 연구 결과들이 발표되고 있다. 이번 종설에서는 PVS와 EPVS가 가지는 임상적 의의와 병태 생리에 대한 최근 문헌을 고찰하고, MRI를 이용한 정성적 평가 및 최적화에 대해 논의해 보고자 한다.

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Structure and function of the perivascular fluid compartment and vertebral venous plexus: Illumining a novel theory on mechanisms underlying the pathogenesis of Alzheimer's, cerebral small vessel, and neurodegenerative diseases

Cited by 10 publications

References 240 publications

Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

EK100 and Antrodin C Improve Brain Amyloid Pathology in APP/PS1 Transgenic Mice by Promoting Microglial and Perivascular Clearance Pathways

An Enlarged Perivascular Space: Clinical Relevance and the Role of Imaging in Aging and Neurologic Disorders

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