Skip to main content

Matrix metalloproteinase-9 is associated with blood-brain barrier opening and brain edema formation after cortical contusion in rats

  • Conference paper
Brain Edema XIII

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 96))

Summary

Matrix metalloproteinases (MMPs) are associated with blood-brain opening and may be involved in the pathophysiology of acute brain injury. Previous research demonstrated that knockout mice de- ficient in MMP-9 subjected to transient focal cerebral ischemia had reduced blood-brain barrier (BBB) disruption and attenuated cerebral infarction.

In this study, we examined MMP-9 up-regulation, BBB disruption, and brain edema formation after cortical impact injury in rats. Cortical contusion was induced by controlled cortical impact. Animals were sacrificed at intervals after injury. MMP up-regulation was assessed by gelatin zymography, and BBB integrity was evaluated using Evans blue dye with a spectrophotometric assay. Brain water content was measured by comparing wet and dry weights of each hemisphere as an indicator of brain edema.

Zymograms showed elevated MMP-9 as early as at 3 hours after injury, reaching a maximum at 18 hours. Peak levels of BBB disruption occurred 6 hours after injury. Brain edema became progressively more severe, peaking 24 hours after injury. Compared to control group, treatment with MMP-inhibitor GM6001 signifi- cantly reduced BBB disruption 6 hours and brain water content (85.9 ± 0.5% vs. 82.6 ± 0.3%; p < 0.05) 24 hours after injury. These findings suggest that MMP-9 may contribute to BBB disturbance and subsequent brain edema after traumatic brain injury.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arvin B, Neville LF, Barone FC, Feuerstein GZ (1996) The role of inflammation and cytokines in brain injury. Neurosci Biobehav Rev 20: 445–452

    Article  PubMed  CAS  Google Scholar 

  2. Asahi M, Wang X, Mori T, Sumii T, Jung JC, Moskowitz MA, Fini ME, Lo EH (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 

  3. Colicos MA, Dash PK (1996) Apoptotic morphology of dentate gyrus granule cells following experimental cortical impact injury in rats: possible role in spatial memory deficits. Brain Res 739: 120–131

    Article  PubMed  CAS  Google Scholar 

  4. Fiotti N, Zivadinov R, Altamura N, Nasuelli D, Bratina A, Tommasi MA, Bosco A, Locatelli L, Grop A, Cazzato G, Guamieri G, Giansante C, Zorzon M (2004) MMP-9 microsatellite polymorphism and multiple sclerosis. J Neuroimmunol 152: 147–153

    Article  PubMed  CAS  Google Scholar 

  5. Katayama Y, Maeda T, Koshinaga M, Kawamata T, Tsubokawa T (1995) Role of excitatory amino acid-mediated ionic fluxes in traumatic brain injury. Brain Pathol 5: 427–435

    PubMed  CAS  Google Scholar 

  6. Kawamata T, Katayama Y, Maeda T, Mori T, Aoyama N, Kikuchi T, Uwahodo Y (1997) Antioxidant, OPC-14117, attenuates edema formation and behavioral deficits following cortical contusion in rats. Acta Neurochir [Suppl] 70: 191–193

    CAS  Google Scholar 

  7. Keogh B, Sheahan BJ, Atkins GJ, Mills KH (2003) Inhibition of matrix metalloproteinases ameliorates blood-brain barrier disruption and neuropathological lesions caused by avirulent Semliki Forest virus infection. Vet Immunol Immunopathol 94: 185–190

    Article  PubMed  CAS  Google Scholar 

  8. Mori T, Katayama Y, Kawamata T, et al (1996) Progressive edema formation in contused brain: Role of tissue osmolality and ion concentrations. Adv Neurotrauma Res 8: 15–18

    Google Scholar 

  9. Mori T, Wang X, Kline AE, Siao CJ, Dixon CE, Tsirka SE, Lo EH (2001) Reduced cortical injury and edema in tissue plasminogen activator knockout mice after brain trauma. Neuroreport 12: 4117–4120

    Article  PubMed  CAS  Google Scholar 

  10. Mori T, Wang X, Aoki T, Lo EH (2002) Downregulation of matrix metalloproteinase-9 and attenuation of edema via inhibition of ERK mitogen activated protein kinase in traumatic brain injury. J Neurotrauma 19: 1411–1419

    Article  PubMed  Google Scholar 

  11. Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J Biol Chem 274: 21491–21494

    Article  PubMed  CAS  Google Scholar 

  12. Romanic AM, White RF, Arleth AJ, Ohlstein EH, Barone FC (1998) Matrix metalloproteinase expression increases after cerebral focal ischemia in rats: inhibition of matrix metalloproteinase-9 reduces infarct size. Stroke 29: 1020–1030

    PubMed  CAS  Google Scholar 

  13. Rosenberg GA, Navratil M, Barone F, Feuerstein G (1996) Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. J Cereb Blood Flow Metab 16: 360–366

    Article  PubMed  CAS  Google Scholar 

  14. Uyama O, Okamura N, Yanase M, Narita M, Kawabata K, Sugita M (1988) Quantitative evaluation of vascular permeability in the gerbil brain after transient ischemia using Evans blue fluorescence. J Cereb Blood Flow Metab 8: 282–284

    PubMed  CAS  Google Scholar 

  15. Vecil GG, Larsen PH, Corley SM, Herx LM, Besson A, Goodyer CG, Yong VW (2000) Interleukin-1 is a key regulator of matrix metalloproteinase-9 expression in human neurons in culture and following mouse brain trauma in vivo. J Neurosci Res 61: 212–224

    Article  PubMed  CAS  Google Scholar 

  16. Wang X, Jung J, Asahi M, Chwang W, Russo L, Moskowitz MA, Dixon CE, Fini ME, Lo EH (2000) Effects of matrix metalloproteinase-9 gene knock-out on morphological and motor outcomes after traumatic brain injury. J Neurosci 20: 7037–7042

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag

About this paper

Cite this paper

Shigemori, Y., Katayama, Y., Mori, T., Maeda, T., Kawamata, T. (2006). Matrix metalloproteinase-9 is associated with blood-brain barrier opening and brain edema formation after cortical contusion in rats. In: Hoff, J.T., Keep, R.F., Xi, G., Hua, Y. (eds) Brain Edema XIII. Acta Neurochirurgica Supplementum, vol 96. Springer, Vienna. https://doi.org/10.1007/3-211-30714-1_29

Download citation

  • DOI: https://doi.org/10.1007/3-211-30714-1_29

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-30712-0

  • Online ISBN: 978-3-211-30714-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics