4.5 Article

Lumbar and ventricular CSF concentrations of extracellular matrix proteins before and after shunt surgery in idiopathic normal pressure hydrocephalus

Journal

FLUIDS AND BARRIERS OF THE CNS
Volume 18, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12987-021-00256-1

Keywords

Brevican; Idiopathic normal pressure hydrocephalus; Immunoassay; Mass spectrometry; Matrix metalloproteinase; Neurocan; Shunt surgery; Tissue inhibitor of metalloproteinases

Categories

Funding

  1. University of Gothenburg
  2. Stiftelsen for Gamla Tjanarinnor
  3. Herbert och Karin Jacobssons Stiftelse
  4. Gun och Bertil Stohnes Stiftelse
  5. Swedish Research Council [201802532, 2017-00915]
  6. European Research Council [681712]
  7. Swedish State Support for Clinical Research [ALFGBG-720931]
  8. Alzheimer Drug Discovery Foundation (ADDF), USA [201809-2016862, RDAPB-201809-2016615]
  9. AD Strategic Fund and the Alzheimer's Association [ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21831377-C]
  10. Olav Thon Foundation
  11. Erling-Persson Family Foundation
  12. European Union [860197]
  13. UK Dementia Research Institute at UCL
  14. Swedish Alzheimer Foundation [AF-742881]
  15. Hjarnfonden, Sweden [FO2017-0243, FO2019-0228]
  16. Swedish government
  17. ALF [ALFGBG-715986]
  18. European Union Joint Program for Neurodegenerative Disorders [JPND2019-466-236]
  19. ALF agreement [ALFGBG 720121, 872441]
  20. Edit Jacobson foundation
  21. Rune and Ulla Amlov foundation.

Ask authors/readers for more resources

The study found that levels of CNS-specific proteins brevican and neurocan did not differ between lumbar and ventricular CSF. However, several CNS-unspecific MMPs and TIMP-1 were significantly increased in lumbar CSF, suggesting potential contribution from peripheral tissues. The increase of ECM proteins in CSF following shunt surgery may indicate disrupted ECM dynamics in iNPH that are restored by restitution of CSF dynamics.
Background Idiopathic normal pressure hydrocephalus (iNPH) is a reversible CNS disease characterized by disturbed cerebrospinal fluid (CSF) dynamics. Changes in the extracellular matrix (ECM) composition might be involved in the pathophysiology of iNPH. The aim of this study was to explore possible differences between lumbar and ventricular CSF concentrations of the ECM markers brevican and neurocan, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and their relation to clinical symptoms in iNPH patients before and after shunt surgery. Methods Paired lumbar and ventricular CSF was collected from 31 iNPH patients, before and four months after shunt surgery. CSF was analysed for concentrations of tryptic peptides originating from brevican and neurocan using a mass spectrometry-based panel, and for MMP-1, -2, -9, -10 and TIMP-1 using fluorescent or electrochemiluminescent immunoassays. Results Brevican and neurocan peptide levels were not influenced by CSF origin, but MMP-1, -2, -10 and TIMP-1 were increased (p <= 0.0005), and MMP-9 decreased (p <= 0.0003) in lumbar CSF compared with ventricular CSF. There was a general trend of ECM proteins to increase following shunt surgery. Ventricular TIMP-1 was inversely correlated with overall symptoms (rho = - 0.62, p < 0.0001). CSF concentrations of the majority of brevican and neurocan peptides were increased in iNPH patients with a history of cardiovascular disease (p <= 0.001, AUC = 0.84-0.94) compared with those without. Conclusion Levels of the CNS-specific proteins brevican and neurocan did not differ between the lumbar and ventricular CSF, whereas the increase of several CNS-unspecific MMPs and TIMP-1 in lumbar CSF suggests contribution from peripheral tissues. The increase of ECM proteins in CSF following shunt surgery could indicate disturbed ECM dynamics in iNPH that are restored by restitution of CSF dynamics.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available