Browsing by Subject "Enlarged perivascular spaces"

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    Brain endothelial cell activation and dysfunction associate with and contribute to the development of enlarged perivascular spaces and cerebral small vessel disease
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Hayden, Melvin Ray
    Multiple injurious stimuli to the brain’s endothelium results in brain endothelial cell activation and dysfunction (BECact/dys) with upregulation of inflammatory signaling cascades and a decrease in bioavailable nitric oxide respectively. These injurious stimuli initiate a brain injury and a response to injury wound healing genetically programed cascade of events, which result in cellular remodeling of the neurovascular unit and blood-brain barrier with increased inflammation and permeability. These remodeling changes also include the perivascular spaces that become dilated to form enlarged perivascular spaces (EPVS) that may be identified noninvasively by magnetic resonance imaging. These EPVS are associated with and considered to be a biomarker for cerebral small vessel disease (SVD) and a dysfunctional glymphatic system with impaired removal of neurotoxic waste, which ultimately results in neurodegeneration with impaired cognition and dementia. The penultimate section discusses the understudied role of venous cerebral circulation in relation to EPVS, SVD, and the vascular contribution to cognitive impairment (VCID). The focus of this review will be primarily on BECact/dys that associates with and contributes to the development of EPVS, SVD, and impaired glymphatic system efflux. Importantly, BECact/dys may be a key piece of the puzzle to unlock this complicated story of EPVS and SVD. Multiple transmission electron micrographs and illustrations will be utilized to depict anatomical ultrastructure and allow for the discussion of multiple functional molecular cascades.
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    Open Access
    The integrity of perivascular spaces is absolutely essential for proper function of the glymphatic system waste and excess water removal from the brain
    (2025) Neetu Tyagi; Melvin R. Hayden; Biología Celular e Histología
    Interest in normal perivascular spaces (PVS) and their evolution to a pathogenic, remodeled enlarged perivascular spaces (EPVS) have increased in parallel with the recently described glymphatic system pathway (GS) during the past decade. EPVS on magnetic resonance images have been shown to be a biomarker for neurovascular, neuroinflammatory, and neuro-degenerative diseases. Thus, the integrity of the PVS is absolutely essential for the proper function of the GS. The mechanisms involved in the evolution of PVS to EPVS are a hot topic in research and as we better understand the pericapillary venules and vein’s role regarding the GS via higher resolution imaging some of the missing pieces of this puzzle will evolve. The GS is currently known to absolutely depend on the brain’s existing PVS to provide a channel for the efflux of neurotoxic substances such as accumulated neuro-degenerative misfolded proteins, proinflammatory cytokines/chemokines, leukocytes, and metabolic, proteolytic debris. The perivascular unit contains both the normal PVS and the pathologic remodeled EPVS and allows for a space to house incoming leukocytes to undergo excessive cellular crosstalk of leukocytes and the resident perivascular macrophage to result in neuroinflammation. Additionally, the polarized aquaporin 4 water channels are essential in waste and excess water removal by the GS.