Journal
JOURNAL OF NEUROSCIENCE RESEARCH
Volume 89, Issue 5, Pages 718-728Publisher
WILEY
DOI: 10.1002/jnr.22594
Keywords
neurovascular unit; blood-spinal cord barrier; G93A; ALS
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Funding
- Ministry of Education, Science, Culture and Sports of Japan [21390267]
- Research Committee of CNS Degenerative Diseases
- Ministry of Health, Labour and Welfare of Japan
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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. (C) 2011 Wiley-Liss, Inc.
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