Skip to main content

Advertisement

Log in

Different roles of matrix metalloproteinases-2 and -9 after human ischaemic stroke

  • Original
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Accumulating data suggest that matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9, are deleterious after acute ischaemic stroke. A beneficial effect of MMPs in the repairing phases of cerebral ischaemia has also been proposed. This study investigated the relationship between MMP-2 and MMP-9 and stroke subtypes, clinical recovery and haemorrhagic transformation (HT). We measured MMP-9 and MMP-2 plasma levels in 29 patients with ischaemic stroke at days one and seven. MMP-2 levels increased only in lacunar strokes, whilst MMP-9 increased only in patients with more severe stroke. Basal MMP-2 levels were higher in patients with stable or recovering symptoms whilst MMP-9 values at day seven were correlated with worse clinical outcome. No differences related to the presence of HT were found. This study sustains a different behaviour of MMPs after ischaemic stroke. MMP-2 seems to be expressed early and related to better outcome, whilst MMP-9 seems to be late and related to more severe stroke.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Rosenberg GA (2002) Matrix metalloproteinases in neuroinflammation. Glia 39:279–291

    Article  PubMed  Google Scholar 

  2. Fatar M, Stroick M, Griebe M, Hennerici M (2005) Matrix metalloproteinases in cerebrovascular diseases. Cerebrovasc Dis 20:141–151

    Article  PubMed  CAS  Google Scholar 

  3. Rosenberg GA, Estrada EY, Dencoff JE (1998) Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain. Stroke 29:2189–2195

    PubMed  CAS  Google Scholar 

  4. Nelson R (2005) Novel MMP inhibitor has potential for treatment of stroke. Lancet Neurol 4:530

    Article  PubMed  Google Scholar 

  5. Lapchak PA, Araujo DM (2001) Reducing bleeding complications after thrombolytic therapy for stroke: clinical potential of metalloproteinase inhibitors and spin trap agents. CNS Drugs 15:819–829

    Article  PubMed  CAS  Google Scholar 

  6. Zhao BQ, Wang S, Kim HY et al (2006) Role of matrix metalloproteinases in delayed cortical responses after stroke. Nat Med 12:441–445

    Article  PubMed  CAS  Google Scholar 

  7. Cunningham LA, Wetzel M, Rosenberg GA (2005) Multiple roles for MMPs and TIMPs in cerebral ischemia. Glia 50:329–339

    Article  PubMed  Google Scholar 

  8. Bamford J, Sandercock P, Dennis M et al (1991) Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 337:1521–1526

    Article  PubMed  CAS  Google Scholar 

  9. Adams HP Jr, Bendixen BH, Kappelle LJ et al (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24:35–41

    PubMed  Google Scholar 

  10. Brott T, Adams HP Jr, Olinger CP et al (1989) Measurements of acute cerebral infarction: a clinical examination scale. Stroke 20:864–870.

    PubMed  CAS  Google Scholar 

  11. Van Swieten JC, Koudstaal PJ, Visser MC et al (1988) Interobserver agreement for the assessment of handicap in stroke patients. Stroke 19:604–607

    PubMed  Google Scholar 

  12. Asahi M, Wang X, Mori T et al (2001) Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia. J Neurosci 21:7724–7732

    PubMed  CAS  Google Scholar 

  13. Montaner J, Alvarez-Sabin J, Molina C et al (2001) Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment. Stroke 32:1759–1766

    PubMed  CAS  Google Scholar 

  14. Horstmann S, Kalb P, Koziol J et al (2003) Profiles of matrix metalloproteinases, their inhibitors, and laminin in stroke patients: influence of different therapies. Stroke 34:2165–2170

    Article  PubMed  Google Scholar 

  15. Montaner J, Molina CA, Monasterio J et al (2003) Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke. Circulation 107:598–603

    Article  PubMed  CAS  Google Scholar 

  16. Montaner J, Alvarez-Sabin J, Molina CA et al (2001) Matrix metalloproteinase expression is related to hemorrhagic transformation after cardioembolic stroke. Stroke 32:2762–2767

    PubMed  CAS  Google Scholar 

  17. Kim YS, Lee KY, Koh SH et al (2006) The role of matrix metalloproteinase 9 in early neurological worsening of acute lacunar infarction. Eur Neurol 55:11–15

    Article  PubMed  CAS  Google Scholar 

  18. Montaner J, Rovira A, Molina CA et al (2003) Plasmatic level of neuroinflammatory markers predict the extent of diffusion-weighted image lesions in hyperacute stroke. J Cereb Blood Flow Metab 23:1403–1407

    Article  PubMed  CAS  Google Scholar 

  19. Rosell A, Alvarez-Sabin J, Arenillas JF et al (2005) A matrix metalloproteinase protein array reveals a strong relation between MMP-9 and MMP-13 with diffusion-weighted image lesion increase in human stroke. Stroke 36:1415–1420

    Article  PubMed  CAS  Google Scholar 

  20. Castellanos M, Leira R, Serena J, Davalos A (2003) Plasma metalloprotinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke 34:40–46

    Article  PubMed  CAS  Google Scholar 

  21. Vukasovic I, Tesija-Kuna A, Topic E et al (2006) Matrix metalloproteinases and their inhibitors in different acute stroke subtypes. Clin Chem Lab Med 44:428–434

    Article  PubMed  CAS  Google Scholar 

  22. Clark AW, Krekoski CA, Bou SS et al (1997) Increased gelatinase A (MMP-2) and gelatinase B (MMP-9) activities in human brain after focal ischemia. Neurosci Lett 238:53–56

    Article  PubMed  CAS  Google Scholar 

  23. Jourquin J, Tremblay E, Decanis N et al (2003) Neuronal activity-dependent increase of net matrix metalloproteinase activity is associated with MMP-9 neurotoxicity after kainate. Eur J Neurosci 18:1507–1517

    Article  PubMed  Google Scholar 

  24. Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839

    Article  PubMed  CAS  Google Scholar 

  25. Jian Liu K, Rosenberg GA (2005) Matrix metalloproteinases and free radicals in cerebral ischemia. Free Radic Biol Med 39:71–80

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to F. Federico.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lucivero, V., Prontera, M., Mezzapesa, D.M. et al. Different roles of matrix metalloproteinases-2 and -9 after human ischaemic stroke. Neurol Sci 28, 165–170 (2007). https://doi.org/10.1007/s10072-007-0814-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-007-0814-0

Key words

Navigation