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Matrix metalloproteinases are associated with increased blood-brain barrier opening in vascular cognitive impairment
Candelario-Jalil E, Thompson J, Taheri S, Grossetete M, Adair JC, Edmonds E, Prestopnik J, Wills J et al.. Stroke, 2011-03-31
Topic: Brain proteins, microglia and lab models
Background and purpose Subcortical ischemic vascular disease (SIVD) is a major form of vascular cognitive impairment (VCI) due to small vessel disease. Matrix metalloproteinases (MMPs) are neutral proteases that disrupt the blood-brain barrier and degrade myelin basic protein under conditions of neuroinflammation. Brain tissues and cerebrospinal fluid (CSF) of patients with VCI have increased levels of MMPs. We hypothesized that patients with SIVD have increased MMPs in the CSF, which are associated with increased CSF albumin. Methods We studied 60 patients with suspected VCI. Twenty-five were classified as SIVD, whereas other groups included mixed Alzheimer disease and VCI, multiple strokes, and leukoaraiosis when white matter lesions were present and the diagnosis of VCI was uncertain. MMP-2 and MMP-9 in CSF and plasma were measured by gel zymography and indexed to CSF and plasma albumin. MMP-3 activity was measured by fluorescent assay. Results We found reduced MMP-2 index (P<0.001) in the CSF for the full group of patients (SIVD, multiple strokes, mixed Alzheimer disease and VCI, and leukoaraiosis) compared with control subjects, whose CSF was obtained during spinal anesthesia. MMP-3 activity was increased in VCI compared with control subjects (P<0.01). In SIVD, MMP-2 index showed a negative correlation with albumin index, which was absent with the MMP-9 index. Combining MMP-2 index and MMP-3 activity separated the patients with SIVD from the control subjects with high specificity (P<0.0005). Conclusions Our results support the hypothesis that MMPs are associated with increased CSF albumin and suggest that they may contribute to the pathophysiology of SIVD.
Key findings
- We hypothesized that patients with SIVD have increased MMPs in the CSF, which are associated with increased CSF albumin.
- Results We found reduced MMP-2 index (P<0.001) in the CSF for the full group of patients (SIVD, multiple strokes, mixed Alzheimer disease and VCI, and leukoaraiosis) compared with control subjects, whose CSF was obtained during spinal anesthesia.
- MMP-3 activity was increased in VCI compared with control subjects (P<0.01).
- Conclusions Our results support the hypothesis that MMPs are associated with increased CSF albumin and suggest that they may contribute to the pathophysiology of SIVD.
Study details
- Participants60
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Stroke) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 60 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21454822) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Candelario-Jalil, E., Thompson, J., Taheri, S., Grossetete, M., Adair, J. C., Edmonds, E., et al. (2011). Matrix metalloproteinases are associated with increased blood-brain barrier opening in vascular cognitive impairment. Stroke. https://doi.org/10.1161/strokeaha.110.600825
Vancouver
Candelario-Jalil E, Thompson J, Taheri S, Grossetete M, Adair JC, Edmonds E, et al. Matrix metalloproteinases are associated with increased blood-brain barrier opening in vascular cognitive impairment. Stroke. 2011. doi:10.1161/strokeaha.110.600825. PMID: 21454822.
BibTeX
@article{candelariojalil2011-21454822,
author = {Candelario-Jalil, E. and Thompson, J. and Taheri, S. and Grossetete, M. and Adair, J. C. and Edmonds, E. and Prestopnik, J. and Wills, J. and others},
title = {{Matrix metalloproteinases are associated with increased blood-brain barrier opening in vascular cognitive impairment}},
journal = {Stroke},
year = {2011},
doi = {10.1161/strokeaha.110.600825},
pmid = {21454822},
url = {https://doi.org/10.1161/strokeaha.110.600825}
}