Aberrant neurogliovascular unit dynamics in cerebral small vessel disease: A rheological clue to vascular Parkinsonism

Che Mohd Nassir, Che Mohd Nasril and Damodaran, Thenmoly and Yusof, Siti R. and Norazit, Anwar and Chilla, Geetha and Huen, Isaac and Bhanu Prakash, K. N. and Mohamed Ibrahim, Norlinah and Mustapha, Muzaimi (2021) Aberrant neurogliovascular unit dynamics in cerebral small vessel disease: A rheological clue to vascular Parkinsonism. Pharmaceutics, 13 (8). ISSN 1999-4923, DOI https://doi.org/10.3390/pharmaceutics13081207.

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The distinctive anatomical assemble and functionally discrete multicellular cerebrovasculature dynamics confer varying rheological and blood-brain barrier permeabilities to preserve the integrity of cerebral white matter and its neural microenvironment. This homeostasis intricately involves the glymphatic system that manages the flow of interstitial solutes, metabolic waste, and clearance through the venous circulation. As a physiologically integrated neurogliovascular unit (NGVU) serving a particularly vulnerable cerebral white matter (from hypoxia, metabolic insults, infection, and inflammation), a likely insidious process over a lifetime could inflict microenvironment damages that may lead to pathological conditions. Two such conditions, cerebral small vessel disease (CSVD) and vascular parkinsonism (VaP), with poorly understood pathomechanisms, are frequently linked to this brain-wide NGVU. VaP is widely regarded as an atypical parkinsonism, described by cardinal motor manifestations and the presence of cerebrovascular disease, particularly white matter hyperintensities (WMHs) in the basal ganglia and subcortical region. WMHs, in turn, are a recognised imaging spectrum of CSVD manifestations, and in relation to disrupted NGVU, also include enlarged perivascular spaces. Here, in this narrative review, we present and discuss on recent findings that argue for plausible clues between CSVD and VaP by focusing on aberrant multicellular dynamics of a unique integrated NGVU-a crossroad of the immune-vascular-nervous system-which may also extend fresher insights into the elusive interplay between cerebral microvasculature and neurodegeneration, and the potential therapeutic targets.

Item Type: Article
Funders: Universiti Sains Malaysia
Uncontrolled Keywords: Cerebral small vessel disease;Vascular Parkinsonism; Homeostasis;Neurogliovascular unit;Glymphatic system
Subjects: R Medicine
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 17 Jun 2022 02:21
Last Modified: 17 Jun 2022 02:21
URI: http://eprints.um.edu.my/id/eprint/34218

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