{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:58:28Z","timestamp":1792277908726,"version":"4.4.0"},"reference-count":203,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The distinctive anatomical assemble and functionally discrete multicellular cerebrovasculature dynamics confer varying rheological and blood\u2013brain 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\u2014a crossroad of the immune\u2013vascular\u2013nervous system\u2014which may also extend fresher insights into the elusive interplay between cerebral microvasculature and neurodegeneration, and the potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/pharmaceutics13081207","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T09:35:32Z","timestamp":1628156132000},"page":"1207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Aberrant Neurogliovascular Unit Dynamics in Cerebral Small Vessel Disease: A Rheological Clue to Vascular Parkinsonism"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-4565","authenticated-orcid":false,"given":"Che Mohd Nasril","family":"Che Mohd Nassir","sequence":"first","affiliation":[{"name":"Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2402-7465","authenticated-orcid":false,"given":"Thenmoly","family":"Damodaran","sequence":"additional","affiliation":[{"name":"Centre for Drug Research, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2257-9933","authenticated-orcid":false,"given":"Siti R.","family":"Yusof","sequence":"additional","affiliation":[{"name":"Centre for Drug Research, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwar","family":"Norazit","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0494-0529","authenticated-orcid":false,"given":"Geetha","family":"Chilla","sequence":"additional","affiliation":[{"name":"A*STAR Institute of Bioengineering and Bioimaging, Helios, 11 Biopolis Way, Singapore 138667, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Huen","sequence":"additional","affiliation":[{"name":"A*STAR Institute of Bioengineering and Bioimaging, Helios, 11 Biopolis Way, Singapore 138667, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhanu Prakash","family":"K. N.","sequence":"additional","affiliation":[{"name":"A*STAR Institute of Bioengineering and Bioimaging, Helios, 11 Biopolis Way, Singapore 138667, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norlinah","family":"Mohamed Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8404-0506","authenticated-orcid":false,"given":"Muzaimi","family":"Mustapha","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"},{"name":"Hospital Universiti Sains Malaysia, Jalan Raja Perempuan Zainab II, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1152\/physrev.00042.2016","article-title":"Physiology of astroglia","volume":"98","author":"Verkhratsky","year":"2018","journal-title":"Physiol. 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