How does neurovascular unit dysfunction contribute to multiple sclerosis?
Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system (CNS) and the most common non-traumatic cause of neurological disability in young adults. Multiple sclerosis clinical care has improved considerably due to the development of disease-modifying therapies that ef...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996123000426 |
| _version_ | 1811165438444306432 |
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| author | Jake M. Cashion Kaylene M. Young Brad A. Sutherland |
| author_facet | Jake M. Cashion Kaylene M. Young Brad A. Sutherland |
| author_sort | Jake M. Cashion |
| collection | DOAJ |
| description | Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system (CNS) and the most common non-traumatic cause of neurological disability in young adults. Multiple sclerosis clinical care has improved considerably due to the development of disease-modifying therapies that effectively modulate the peripheral immune response and reduce relapse frequency. However, current treatments do not prevent neurodegeneration and disease progression, and efforts to prevent multiple sclerosis will be hampered so long as the cause of this disease remains unknown. Risk factors for multiple sclerosis development or severity include vitamin D deficiency, cigarette smoking and youth obesity, which also impact vascular health. People with multiple sclerosis frequently experience blood-brain barrier breakdown, microbleeds, reduced cerebral blood flow and diminished neurovascular reactivity, and it is possible that these vascular pathologies are tied to multiple sclerosis development. The neurovascular unit is a cellular network that controls neuroinflammation, maintains blood-brain barrier integrity, and tightly regulates cerebral blood flow, matching energy supply to neuronal demand. The neurovascular unit is composed of vessel-associated cells such as endothelial cells, pericytes and astrocytes, however neuronal and other glial cell types also comprise the neurovascular niche. Recent single-cell transcriptomics data, indicate that neurovascular cells, particular cells of the microvasculature, are compromised within multiple sclerosis lesions. Large-scale genetic and small-scale cell biology studies also suggest that neurovascular dysfunction could be a primary pathology contributing to multiple sclerosis development. Herein we revisit multiple sclerosis risk factors and multiple sclerosis pathophysiology and highlight the known and potential roles of neurovascular unit dysfunction in multiple sclerosis development and disease progression. We also evaluate the suitability of the neurovascular unit as a potential target for future disease modifying therapies for multiple sclerosis. |
| first_indexed | 2024-04-10T15:37:09Z |
| format | Article |
| id | doaj.art-e0abc73da0d14c3983311cf6163b45a4 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-10T15:37:09Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-e0abc73da0d14c3983311cf6163b45a42023-02-13T04:06:57ZengElsevierNeurobiology of Disease1095-953X2023-03-01178106028How does neurovascular unit dysfunction contribute to multiple sclerosis?Jake M. Cashion0Kaylene M. Young1Brad A. Sutherland2Tasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, AustraliaMenzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania 7000, AustraliaTasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia; Corresponding author at: Level 4, Medical Sciences Precinct, Tasmanian School of Medicine, University of Tasmania, Hobart TAS 7000, Australia.Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system (CNS) and the most common non-traumatic cause of neurological disability in young adults. Multiple sclerosis clinical care has improved considerably due to the development of disease-modifying therapies that effectively modulate the peripheral immune response and reduce relapse frequency. However, current treatments do not prevent neurodegeneration and disease progression, and efforts to prevent multiple sclerosis will be hampered so long as the cause of this disease remains unknown. Risk factors for multiple sclerosis development or severity include vitamin D deficiency, cigarette smoking and youth obesity, which also impact vascular health. People with multiple sclerosis frequently experience blood-brain barrier breakdown, microbleeds, reduced cerebral blood flow and diminished neurovascular reactivity, and it is possible that these vascular pathologies are tied to multiple sclerosis development. The neurovascular unit is a cellular network that controls neuroinflammation, maintains blood-brain barrier integrity, and tightly regulates cerebral blood flow, matching energy supply to neuronal demand. The neurovascular unit is composed of vessel-associated cells such as endothelial cells, pericytes and astrocytes, however neuronal and other glial cell types also comprise the neurovascular niche. Recent single-cell transcriptomics data, indicate that neurovascular cells, particular cells of the microvasculature, are compromised within multiple sclerosis lesions. Large-scale genetic and small-scale cell biology studies also suggest that neurovascular dysfunction could be a primary pathology contributing to multiple sclerosis development. Herein we revisit multiple sclerosis risk factors and multiple sclerosis pathophysiology and highlight the known and potential roles of neurovascular unit dysfunction in multiple sclerosis development and disease progression. We also evaluate the suitability of the neurovascular unit as a potential target for future disease modifying therapies for multiple sclerosis.http://www.sciencedirect.com/science/article/pii/S0969996123000426Neurovascular unitMultiple sclerosisEndothelial cellsAstrocytesPericytes |
| spellingShingle | Jake M. Cashion Kaylene M. Young Brad A. Sutherland How does neurovascular unit dysfunction contribute to multiple sclerosis? Neurobiology of Disease Neurovascular unit Multiple sclerosis Endothelial cells Astrocytes Pericytes |
| title | How does neurovascular unit dysfunction contribute to multiple sclerosis? |
| title_full | How does neurovascular unit dysfunction contribute to multiple sclerosis? |
| title_fullStr | How does neurovascular unit dysfunction contribute to multiple sclerosis? |
| title_full_unstemmed | How does neurovascular unit dysfunction contribute to multiple sclerosis? |
| title_short | How does neurovascular unit dysfunction contribute to multiple sclerosis? |
| title_sort | how does neurovascular unit dysfunction contribute to multiple sclerosis |
| topic | Neurovascular unit Multiple sclerosis Endothelial cells Astrocytes Pericytes |
| url | http://www.sciencedirect.com/science/article/pii/S0969996123000426 |
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