Effects of traumatic brain injury on sleep and enlarged perivascular spaces

Opel, Ryan A.; Christy, Alison; Boespflug, Erin L.; Weymann, Kris; Case, Brendan; Pollock, Jeffery M.; Silbert, Lisa C.; Lim, Miranda M.

doi:10.1177/0271678x18791632

Cited by 53 publications

(51 citation statements)

References 41 publications

(46 reference statements)

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“…Normally, the diameter cutoff of PVS is set as 3 mm ( Zhu et al, 2011 ; Wardlaw et al, 2013 , 2020 ; Dubost et al, 2019 ). Previous studies demonstrated that EPVS was linked to impaired glymphatic clearance ( Mestre et al, 2017 ; Boespflug et al, 2018 ; Opel et al, 2019 ). The GS dysfunction contributes to the accumulation of metabolic wastes and neurotoxic substances in PVS, ultimately resulting in EPVS ( Figure 1C ).…”

Section: The Gs Dysfunction In Strokementioning

confidence: 99%

The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment

Zhao

et al. 2021

Front. Aging Neurosci.

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The glymphatic system (GS) is a novel defined brain-wide perivascular transit network between cerebrospinal fluid (CSF) and interstitial solutes that facilitates the clearance of brain metabolic wastes. The complicated network of the GS consists of the periarterial CSF influx pathway, astrocytes-mediated convective transport of fluid and solutes supported by AQP4 water channels, and perivenous efflux pathway. Recent researches indicate that the GS dysfunction is associated with various neurological disorders, including traumatic brain injury, hydrocephalus, epilepsy, migraine, and Alzheimer’s disease (AD). Meanwhile, the GS also plays a pivotal role in the pathophysiological process of stroke, including brain edema, blood–brain barrier (BBB) disruption, immune cell infiltration, neuroinflammation, and neuronal apoptosis. In this review, we illustrated the key anatomical structures of the GS, the relationship between the GS and the meningeal lymphatic system, the interaction between the GS and the BBB, and the crosstalk between astrocytes and other GS cellular components. In addition, we contributed to the current knowledge about the role of the GS in the pathology of stroke and the role of AQP4 in stroke. We further discussed the potential use of the GS in early risk assessment, diagnostics, prognostics, and therapeutics of stroke.

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Section: The Gs Dysfunction In Strokementioning

confidence: 99%

The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment

Zhao

et al. 2021

Front. Aging Neurosci.

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“…Pathophysiological mechanisms of TBI that result in AD-like neurodegenerative processes remain poorly understood, but neuroinflammation leading to neurodegeneration is a likely candidate. AD pathology is characterized by intra-neuronal neurofibrillary tangles of hyperphosphorylated tau (p-tau) and deposits of extracellular Aβ, which likely relate to the dysfunction of brain clearance mechanisms ( 88 , 89 ). Aβ deposition is regulated by an equilibrium between Aβ production and clearance.…”

Section: Neuropathology Of Tbimentioning

confidence: 99%

“…Low levels of brain-derived biomarkers in blood may be attributed to factors such as proteolytic degradation and low permeability of the BBB ( 160 ). Furthermore, clearance of interstitial proteins depends in part on the glymphatic system ( 161 ), which is dysfunctional after TBI ( 89 ), likely contributing to discrepancies between levels of biomarker proteins in the brain and blood.…”

Section: Extracellular Vesicles In Tbimentioning

confidence: 99%

Extracellular Vesicle Proteins and MicroRNAs as Biomarkers for Traumatic Brain Injury

et al. 2020

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Traumatic brain injury (TBI) is a heterogeneous condition, associated with diverse etiologies, clinical presentations and degrees of severity, and may result in chronic neurobehavioral sequelae. The field of TBI biomarkers is rapidly evolving to address the many facets of TBI pathology and improve its clinical management. Recent years have witnessed a marked increase in the number of publications and interest in the role of extracellular vesicles (EVs), which include exosomes, cell signaling, immune responses, and as biomarkers in a number of pathologies. Exosomes have a well-defined lipid bilayer with surface markers that reflect the cell of origin and an aqueous core that contains a variety of biological material including proteins (e.g., cytokines and growth factors) and nucleic acids (e.g., microRNAs). The presence of proteins associated with neurodegenerative changes such as amyloid-β, α-synuclein and phosphorylated tau in exosomes suggests a role in the initiation and propagation of neurological diseases. However, mechanisms of cell communication involving exosomes in the brain and their role in TBI pathology are poorly understood. Exosomes are promising TBI biomarkers as they can cross the blood-brain barrier and can be isolated from peripheral fluids, including serum, saliva, sweat, and urine. Exosomal content is protected from enzymatic degradation by exosome membranes and reflects the internal environment of their cell of origin, offering insights into tissue-specific pathological processes. Challenges in the clinical use of exosomal cargo as biomarkers include difficulty in isolating pure exosomes, variable yields of the isolation processes, quantification of vesicles, and lack of specificity of exosomal markers. Moreover, there is no consensus regarding nomenclature and characteristics of EV subtypes. In this review, we discuss current technical limitations and challenges of using exosomes and other EVs as blood-based biomarkers, highlighting their potential as diagnostic and prognostic tools in TBI.

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“…They are an essential pathway of the brain’s glymphatic system which plays an important role in clearing metabolic wastes from the brain ( Iliff et al, 2012 ; Rasmussen et al, 2018 ). Increased number of MRI-visible PVSs has been widely reported in patients compared to healthy controls, including those with Alzheimer’s disease ( Boespflug et al, 2018b ; Cai et al, 2015 ; Chen et al, 2011 ; Hansen et al, 2015 ), multiple sclerosis ( Kilsdonk et al, 2015 ; Wuerfel et al, 2008 ), traumatic brain injury (TBI) ( Inglese et al, 2005 ), small vessel disease (SVD) ( Doubal et al, 2010 ; Duperron et al, 2018 ; Zhu et al, 2010 ), stroke ( Park et al, 2019a ), and sleep disturbance ( Opel et al, 2019 ; Song et al, 2017 ), suggesting that the diseased conditions can lead to enlargement of PVSs. In addition to association with current diseases, higher numbers of PVSs were also associated with increased risks of future SVD ( Ding et al, 2017 ), stroke ( Duperron et al, 2019 ; Gutierrez et al, 2017 ), recurrence of transient ischemic attack ( Lau et al,2017 ), cognitive decline ( Ding et al, 2017 ; Park et al, 2019b ), and development of subdural fluid accumulation in mild TBI patients ( Koo et al, 2019 ), suggesting that PVS imaging may have potential prognostic values.…”

Section: Introductionmentioning

confidence: 99%

Morphology of perivascular spaces and enclosed blood vessels in young to middle-aged healthy adults at 7T: Dependences on age, brain region, and breathing gas

et al. 2020

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Perivascular spaces (PVSs) are fluid-filled spaces surrounding penetrating blood vessels in the brain and are an integral pathway of the glymphatic system. A PVS and the enclosed blood vessel are commonly visualized as a single vessel-like complex (denoted as PVSV) in high-resolution MRI images. Quantitative characterization of the PVSV morphology in MRI images in healthy subjects may serve as a reference for detecting disease related PVS and/or blood vessel alterations in patients with brain diseases. To this end, we evaluated the age dependences, spatial heterogeneities, and dynamic properties of PVSV morphological features in 45 healthy subjects (21–55 years old), using an ultra-high-resolution three-dimensional transverse relaxation time weighted MRI sequence (0.41 × 0.41 × 0.4 mm 3 ) at 7T. Quantitative PVSV parameters, including apparent diameter, count, volume fraction (VF), and relative contrast to noise ratio (rCNR) were calculated in the white matter and subcortical structures. Dynamic changes were induced by carbogen breathing which are known to induce vasodilation and increase the blood oxygenation level in the brain. PVSV count and VF significantly increased with age in basal ganglia (BG), so did rCNR in BG, midbrain, and white matter (WM). Apparent PVSV diameter also showed a positive association with age in the three brain regions, although it did not reach statistical significance. The PVSV VF and count showed large inter-subject variations, with coefficients of variation ranging from 0.17 to 0.74 after regressing out age and gender effects. Both apparent diameter and VF exhibited significant spatial heterogeneity, which cannot be explained solely by radio-frequency field inhomogeneities. Carbogen breathing significantly increased VF in BG and WM, and rCNR in thalamus, BG, and WM compared to air breathing. Our results are consistent with gradual dilation of PVSs with age in healthy adults. The PVSV morphology exhibited spatial heterogeneity and large inter-subject variations and changed during carbogen breathing compared to air breathing.

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Effects of traumatic brain injury on sleep and enlarged perivascular spaces

Cited by 53 publications

References 41 publications

The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment

The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment

Extracellular Vesicle Proteins and MicroRNAs as Biomarkers for Traumatic Brain Injury

Morphology of perivascular spaces and enclosed blood vessels in young to middle-aged healthy adults at 7T: Dependences on age, brain region, and breathing gas

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