Disruption of neurovascular unit prior to motor neuron degeneration in amyotrophic lateral sclerosis
Abstract
Recent reports suggest that functional or structural defect of vascular components are implicated in amyotrophic lateral sclerosis (ALS) pathology. In the present study, we examined a possible change of the neurovascular unit consisting of endothelium (PCAM‐1), tight junction (occludin), and basement membrane (collagen IV) in relation to a possible activation of MMP‐9 in ALS patients and ALS model mice. We found that the damage in the neurovascular unit was more prominent in the outer side and preferentially in the anterior horn of ALS model mice. This damage occurred prior to motor neuron degeneration and was accompanied by MMP‐9 up‐regulation. We also found the dissociation between the PCAM‐1‐positive endothelium and GFAP‐positive astrocyte foot processes in both humans and the animal model of ALS. The present results indicate that perivascular damage precedes the sequential changes of the disease, which are held in common between humans and the animal model of ALS, suggesting that the neurovascular unit is a potential target for therapeutic intervention in ALS. © 2011 Wiley‐Liss, Inc.
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Studies in SOD1 transgenic mice expressing dismutase-active (G93A and G37R) and dismutase-inactive (G85R) mutations have suggested that BSCB breakdown occurs before motor neuron injury.
“Studies in SOD1 transgenic mice expressing dismutase-active (G93A and G37R) and dismutase-inactive (G85R) mutations have suggested that BSCB breakdown occurs before motor neuron injury (194, 415, 651, 687, 688).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [415]
BBB disruption including diminished levels of tight junction proteins, IgG and hemosiderin perivascular deposits, and GLUT1 reduction has been shown to precede neuroinflammation, motor neuron loss, and motor impairment in different types of SOD1 mutants.
“BBB disruption including diminished levels of TJ proteins, immunoglobulin G (IgG) and hemosiderin perivascular deposits, and GLUT1 reduction has been shown to precede neuroinflammation, motor neuron loss, and motor impairment in different types of SOD1 mutants (415, 687, 688).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [415]
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- Authors
- Miyazaki, K., Ohta, Y., Nagai, M., Morimoto, N., Kurata, T., Takehisa, Y., Ikeda, Y., Matsuura, T., & Abe, K.
- Affiliations
- Okayama University (JP)
- Corresponding author
- Abe, Koji
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2011-02-17
- Volume
- 89
- Issue
- 5
- Pages
- 718-728
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W1973593092
- Cited by
- 197
- References
- 6
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 14 · 2023: 12 · 2022: 19 · 2021: 25 · 2020: 17 · 2019: 12 · 2018: 12 · 2017: 10 · 2016: 7 · 2015: 9 · 2014: 11 · 2013: 8 · 2012: 16
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (21591083)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Keywords
- amyotrophic lateral sclerosis, neurovascular unit, motor neuron degeneration, MMP-9, occludin, type IV collagen, basement membrane, endothelium, ventral horn, ALS mouse model, therapeutic target
- MeSH terms
- Amyotrophic Lateral Sclerosis, Animals, Blood-Brain Barrier, Disease Models, Animal, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Motor Neurons, Nerve Degeneration, Spinal Cord, Endothelial Cells, Mice
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