Skip to main content
SpringerLink
Log in

Matrix metalloproteinases and inflammatory diseases of the central nervous system

  • Chapter
Matrix Metalloproteinases in Tissue Remodelling and Inflammation

Part of the book series: Progress in Inflammation Research ((PIR))

  • 540 Accesses

Abstract

Matrix metalloproteinases (MMPs) are involved in the pathogenesis of several diseases of the central nervous system (CNS) that share common pathophysiological processes, such as bloodbrain barrier (BBB) disruption, oxidative stress, remodelling of the extracellular matrix (ECM) and inflammation. In ischaemic brain injury, MMPs are implicated in various stages of the disease. MMPs contribute to the disruption of BBB leading to vasogenic oedema and to the influx of leucocytes into the CNS. The ability of MMPs to digest the basal lamina of capillaries increases the risk of haemorrhagic transformation (HT) of the ischaemic tissue. During the acute ischaemic phase, maintenance of the ECM is essential for neuronal survival. However, ECM degradation and its reconstitution are critical to tissue recovery. MMPs, as key modulators of ECM homeostasis, play a role in the cascades leading to neuronal cell death and tissue regeneration. Yet they may have a detrimental or beneficial role depending on the type and the stage of brain injury. This pleiotropic implication of MMPs in brain injury has opened new areas of investigation, which should lead to innovative therapeutic strategies.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
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. Yong VW, Power C, Forsyth P, Edwards DR (2001) Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci 2: 502–511

    PubMed  CAS  Google Scholar 

  2. Yong VW, Krekoski CA, Forsyth PA, Bell R, Edwards DR (1998) Matrix metalloproteinases and diseases of the CNS. Trends Neurosci 21: 75–80

    PubMed  CAS  Google Scholar 

  3. Massova I, Kotra LP, Fridman R, Mobashery S (1998) Matrix metalloproteinases: structures, evolution, and diversification. Faseb J 12: 1075–1095

    PubMed  CAS  Google Scholar 

  4. Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17: 463–516

    PubMed  CAS  Google Scholar 

  5. Gasche Y, Fujimura M, Morita-Fujimura Y, Copin JC, Kawase M, Massengale J, Chan PH (1999) Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood-brain barrier dysfunction. J Cereb Blood Flow Metab 19: 1020–1028

    PubMed  CAS  Google Scholar 

  6. Zhang JW, Gottschall PE (1997) Zymographic measurement of gelatinase activity in brain tissue after detergent extraction and affinity-support purification. J Neurosci Methods 76: 15–20

    PubMed  CAS  Google Scholar 

  7. Fujimura M, Gasche Y, Morita-Fujimura Y, Massengale J, Kawase M, Chan PH (1999) Early appearance of activated matrix metalloproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion. Brain Res 842: 92–100

    PubMed  CAS  Google Scholar 

  8. Overall CM, Wrana JL, Sodek J (1991) Transcriptional and post-transcriptional regulation of 72-kDa gelatinase/type IV collagenase by transforming growth factor-beta 1 in human fibroblasts. Comparisons with collagenase and tissue inhibitor of matrix metalloproteinase gene expression. J Biol Chem 266: 14064–14071

    PubMed  CAS  Google Scholar 

  9. Delany AM, Brinckerhoff CE (1992) Post-transcriptional regulation of collagenase and stromelysin gene expression by epidermal growth factor and dexamethasone in cultured human fibroblasts. J Cell Biochem 50: 400–410

    PubMed  CAS  Google Scholar 

  10. Akool el S, Kleinert H, Hamada FM, Abdelwahab MH, Forstermann U, Pfeilschifter J, Eberhardt W (2003) Nitric oxide increases the decay of matrix metalloproteinase 9 mRNA by inhibiting the expression of mRNA-stabilizing factor HuR. Mol Cell Biol 23: 4901–4916

    CAS  Google Scholar 

  11. Christman JW, Blackwell TS, Juurlink BH (2000) Redox regulation of nuclear factor kappa B: therapeutic potential for attenuating inflammatory responses. Brain Pathol 10: 153–162

    PubMed  CAS  Google Scholar 

  12. Huhtala P, Chow LT, Tryggvason K (1990) Structure of the human type IV collagenase gene. J Biol Chem 265: 11077–11082

    PubMed  CAS  Google Scholar 

  13. Brooks PC, Stromblad S, Sanders LC, von Schalscha TL, Aimes RT, Stetler-Stevenson WG, Quigley JP, Cheresh DA (1996) Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell 85: 683–693

    PubMed  CAS  Google Scholar 

  14. Yu Q, Stamenkovic I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 14: 163–176

    PubMed  Google Scholar 

  15. Yu WH, Woessner JF Jr (2000) Heparan sulfate proteoglycans as extracellular docking molecules for matrilysin (matrix metalloproteinase 7). J Biol Chem 275: 4183–4191

    PubMed  CAS  Google Scholar 

  16. Van Wart HE, Birkedal-Hansen H (1990) The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc Natl Acad Sci USA 87: 5578–5582

    PubMed  Google Scholar 

  17. Stricklin GP, Jeffrey JJ, Roswit WT, Eisen AZ (1983) Human skin fibroblast procollagenase: mechanisms of activation by organomercurials and trypsin. Biochemistry 22: 61–68

    PubMed  CAS  Google Scholar 

  18. Knauper V, Will H, Lopez-Otin C, Smith B, Atkinson SJ, Stanton H, Hembry RM, Murphy G (1996) Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem 271: 17124–17131

    PubMed  CAS  Google Scholar 

  19. Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS (1996) Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest 98: 2572–2579

    PubMed  CAS  Google Scholar 

  20. Weiss SJ, Peppin G, Ortiz X, Ragsdale C, Test ST (1985) Oxidative autoactivation of latent collagenase by human neutrophils. Science 227: 747–749

    PubMed  CAS  Google Scholar 

  21. Tyree B, Seltzer JL, Halme J, Jeffrey JJ, Eisen AZ (1981) The stoichiometric activation of human skin fibroblast pro-collagenase by factors present in human skin and rat uterus. Arch Biochem Biophys 208: 440–443

    PubMed  CAS  Google Scholar 

  22. Gu Z, Kaul M, Yan B, Kridel SJ, Cui J, Strongin A, Smith JW, Liddington RC, Lipton SA (2002) S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science 297: 1186–1190

    PubMed  CAS  Google Scholar 

  23. Kotra LP, Zhang L, Fridman R, Orlando R, Mobashery S (2002) N-Glycosylation pattern of the zymogenic form of human matrix metalloproteinase-9. Bioorg Chem 30: 356–370

    PubMed  CAS  Google Scholar 

  24. Mignatti P, Rifkin DB (1993) Biology and biochemistry of proteinases in tumor invasion. Physiol Rev 73: 161–195

    PubMed  CAS  Google Scholar 

  25. Kleiner DE Jr, Stetler-Stevenson WG (1993) Structural biochemistry and activation of matrix metalloproteases. Curr Opin Cell Biol 5: 891–897

    PubMed  CAS  Google Scholar 

  26. Lohi J, Lehti K, Westermarck J, Kahari VM, Keski-Oja J (1996) Regulation of membrane-type matrix metalloproteinase-1 expression by growth factors and phorbol 12-myristate 13-acetate. Eur J Biochem 239: 239–247

    PubMed  CAS  Google Scholar 

  27. Bergmann U, Tuuttila A, Stetler-Stevenson WG, Tryggvason K (1995) Autolytic activation of recombinant human 72 kilodalton type IV collagenase. Biochemistry 34: 2819–2825

    PubMed  CAS  Google Scholar 

  28. Goldberg GI, Marmer BL, Grant JA, Eisen AZ, Wilhelm S, He C (1989) Human 72k type IV collagenase forms a complex with a tissue inhibitor of metalloproteinase designed TIMP-2. Proc Natl Acad Sci USA 86: 8207–8211

    PubMed  CAS  Google Scholar 

  29. Strongin AY, Collier Y, Bannikov G, Marmer BL, Grant GA, Goldberg GI (1995) Mechanism of cell surface activation of 72-kDa type IV collagenase. J Biol Chem 270: 5331–5338

    PubMed  CAS  Google Scholar 

  30. Strongin AY, Marmer BL, Grant GA, Goldberg GI (1993) Plasma membrane-dependent activation of the 72-kDa type IV collagenase is prevented by complex formation with TIMP-2. J Biol Chem 268: 14033–14039

    PubMed  CAS  Google Scholar 

  31. Willenbrock F, Murphy G (1994) Structure-function relationships in the tissue inhibitors of metalloproteinases. Am J Respir Crit Care Med 150: S165–S170

    PubMed  CAS  Google Scholar 

  32. Dzwonek J, Rylski M, Kaczmarek L (2004) Matrix metalloproteinases and their endogenous inhibitors in neuronal physiology of the adult brain. FEBS Lett 567: 129–135

    PubMed  CAS  Google Scholar 

  33. Vaillant C, Didier-Bazes M, Hutter A, Belin MF, Thomasset N (1999) Spatiotemporal expression patterns of metalloproteinases and their inhibitors in the postnatal developing rat cerebellum. J Neurosci 19: 4994–5004

    PubMed  CAS  Google Scholar 

  34. Wright JW, Masino AJ, Reichert JR, Turner GD, Meighan SE, Meighan PC, Harding JW (2003) Ethanol-induced impairment of spatial memory and brain matrix metalloproteinases. Brain Res 963: 252–261

    PubMed  CAS  Google Scholar 

  35. Zhang JW, Deb S, Gottschall PE (1998) Regional and differential expression of gelatinases in rat brain after systemic kainic acid or bicuculline administration. Eur J Neurosci 10: 3358–3368

    PubMed  CAS  Google Scholar 

  36. Zhang JW, Deb S, Gottschall PE (2000) Regional and age-related expression of gelatinases in the brains of young and old rats after treatment with kainic acid. Neurosci Lett 295: 9–12

    PubMed  CAS  Google Scholar 

  37. 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 

  38. 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

    PubMed  CAS  Google Scholar 

  39. Asahi M, Asahi K, Jung JC, del Zoppo GJ, Fini ME, Lo EH (2000) Role for matrix metalloproteinase 9 after focal cerebral ischemia: effects of gene knockout and enzyme inhibition with BB-94. J Cereb Blood Flow Metab 20: 1681–1689

    PubMed  CAS  Google Scholar 

  40. Heo JH, Lucero J, Abumiya T, Koziol JA, Copeland BR, del Zoppo GJ (1999) Matrix metalloproteinases increase very early during experimental focal cerebral ischemia. J Cereb Blood Flow Metab 19: 624–633

    PubMed  CAS  Google Scholar 

  41. Anthony DC, Ferguson B, Matyzak MK, Miller KM, Esiri MM, Perry VH (1997) Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke. Neuropathol Appl Neurobiol 23: 406–415

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  43. Lewen A, Matz P, Chan PH (2000) Free radical pathways in CNS injury. J Neurotrauma 17: 871–890

    PubMed  CAS  Google Scholar 

  44. Gasche Y, Copin JC, Sugawara T, Fujimura M, Chan PH (2001) Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia. J Cereb Blood Flow Metab 21: 1393–1400

    PubMed  CAS  Google Scholar 

  45. Morita-Fujimura Y, Fujimura M, Gasche Y, Copin JC, Chan PH (2000) Overexpression of copper and zinc superoxide dismutase in transgenic mice prevents the induction and activation of matrix metalloproteinases after cold injury-induced brain trauma. J Cereb Blood Flow Metab 20: 130–138

    PubMed  CAS  Google Scholar 

  46. Gidday JM, Gasche YG, Copin JC, Shah AR, Perez RS, Shapiro SD, Chan PH, Park TS (2005) Leukocyte-derived matrix metalloproteinase-9 mediates blood-brain barrier breakdown and is proinflammatory following transient focal cerebral ischemia. Am J Physiol Heart Circ Physiol 289: H558–568

    PubMed  CAS  Google Scholar 

  47. Rosenberg GA, Cunningham LA, Wallace J, Alexander S, Estrada EY, Grossetete M, Razhagi A, Miller K, Gearing A (2001) Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell cultures. Brain Res 893: 104–112

    PubMed  CAS  Google Scholar 

  48. 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 

  49. Wang X, Barone FC, White RF, Feuerstein GZ (1998) Subtractive cloning identifies tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) increased gene expression following focal stroke. Stroke 29: 516–520

    PubMed  CAS  Google Scholar 

  50. Nguyen M, Arkwell J, Jackson CJ (1998) Active and tissue inhibitor of matrix metalloproteinase-free gelatinase B accumulates within human microvascular endothelial vesicles. J Biol Chem 273: 5400–5404

    PubMed  CAS  Google Scholar 

  51. Cossins JA, Clements JM, Ford J, Miller KM, Pigott R, Vos W, Van der Valk P, De Groot CJ (1997) Enhanced expression of MMP-7 and MMP-9 in demyelinating multiple sclerosis lesions. Acta Neuropathol (Berl) 94: 590–598

    CAS  Google Scholar 

  52. Maeda A, Sobel RA (1996) Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and multiple sclerosis lesions. J Neuropathol Exp Neurol 55: 300–309

    PubMed  CAS  Google Scholar 

  53. Kieseier BC, Kiefer R, Clements JM, Miller K, Wells GM, Schweitzer T, Gearing AJ, Hartung HP (1998) Matrix metalloproteinase-9 and-7 are regulated in experimental autoimmune encephalomyelitis. Brain 121 (Pt 1): 159–166

    PubMed  Google Scholar 

  54. Gijbels K, Masure S, Carton H, Opdenakker G (1992) Gelatinase in the cerebrospinal fluid of patients with multiple sclerosis and other inflammatory neurological disorders. J Neuroimmunol 41: 29–34

    PubMed  CAS  Google Scholar 

  55. Leppert D, Ford J, Stabler G, Grygar C, Lienert C, Huber S, Miller KM, Hauser SL, Kappos L (1998) Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis. Brain 121 (Pt 12): 2327–2334

    PubMed  Google Scholar 

  56. Lee MA, Palace J, Stabler G, Ford J, Gearing A, Miller K (1999) Serum gelatinase B, TIMP-1 and TIMP-2 levels in multiple sclerosis. A longitudinal clinical and MRI study. Brain 122 (Pt 2): 191–197

    PubMed  Google Scholar 

  57. Waubant E, Goodkin DE, Gee L, Bacchetti P, Sloan R, Stewart T, Andersson PB, Stabler G, Miller K (1999) Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis. Neurology 53: 1397–1401

    PubMed  CAS  Google Scholar 

  58. Trojano M, Avolio C, Liuzzi GM, Ruggieri M, Defazio G, Liguori M, Santacroce MP, Paolicelli D, Giuliani F, Riccio P et al (1999) Changes of serum sICAM-1 and MMP-9 induced by rIFNbeta-1b treatment in relapsing-remitting MS. Neurology 53: 1402–1408

    PubMed  CAS  Google Scholar 

  59. Lichtinghagen R, Seifert T, Kracke A, Marckmann S, Wurster U, Heidenreich F (1999) Expression of matrix metalloproteinase-9 and its inhibitors in mononuclear blood cells of patients with multiple sclerosis. J Neuroimmunol 99: 19–26

    PubMed  CAS  Google Scholar 

  60. Cuzner ML, Gveric D, Strand C, Loughlin AJ, Paemen L, Opdenakker G, Newcombe J (1996) The expression of tissue-type plasminogen activator, matrix metalloproteases and endogenous inhibitors in the central nervous system in multiple sclerosis: comparison of stages in lesion evolution. J Neuropathol Exp Neurol 55: 1194–1204

    PubMed  CAS  Google Scholar 

  61. Galboiz Y, Shapiro S, Lahat N, Rawashdeh H, Miller A (2001) Matrix metalloproteinases and their tissue inhibitors as markers of disease subtype and response to interferonbeta therapy in relapsing and secondary-progressive multiple sclerosis patients. Ann Neurol 50: 443–451

    PubMed  CAS  Google Scholar 

  62. Kouwenhoven M, Ozenci V, Tjernlund A, Pashenkov M, Homman M, Press R, Link H (2002) Monocyte-derived dendritic cells express and secrete matrix-degrading metalloproteinases and their inhibitors and are imbalanced in multiple sclerosis. J Neuroimmunol 126: 161–171

    PubMed  CAS  Google Scholar 

  63. Ozenci V, Rinaldi L, Teleshova N, Matusevicius D, Kivisakk P, Kouwenhoven M, Link H (1999) Metalloproteinases and their tissue inhibitors in multiple sclerosis. J Autoimmun 12: 297–303

    PubMed  CAS  Google Scholar 

  64. Paul R, Angele B, Sporer B, Pfister HW, Koedel U (2004) Inflammatory response during bacterial meningitis is unchanged in Fas-and Fas ligand-deficient mice. J Neuroimmunol 152: 78–82

    PubMed  CAS  Google Scholar 

  65. Paul R, Lorenzl S, Koedel U, Sporer B, Vogel U, Frosch M, Pfister HW (1998) Matrix metalloproteinases contribute to the blood-brain barrier disruption during bacterial meningitis. Ann Neurol 44: 592–600

    PubMed  CAS  Google Scholar 

  66. Pugin D, Copin J-C, Goodyear M-C, Landis T, Gasche Y (2006) Persisting vasculitis after pneumococcal meningitis: a possible role for matrix metalloproteinase-9 as a marker of disease. Neurocritical Care 4: 237–240

    PubMed  Google Scholar 

  67. Leppert D, Leib SL, Grygar C, Miller KM, Schaad UB, Hollander GA (2000) Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood-brain barrier damage and neurological sequelae. Clin Infect Dis 31: 80–84

    PubMed  CAS  Google Scholar 

  68. Leib SL, Clements JM, Lindberg RL, Heimgartner C, Loeffler JM, Pfister LA, Tauber MG, Leppert D (2001) Inhibition of matrix metalloproteinases and tumour necrosis factor alpha converting enzyme as adjuvant therapy in pneumococcal meningitis. Brain 124: 1734–1742

    PubMed  CAS  Google Scholar 

  69. Leib SL, Leppert D, Clements J, Tauber MG (2000) Matrix metalloproteinases contribute to brain damage in experimental pneumococcal meningitis. Infect Immun 68: 615–620

    PubMed  CAS  Google Scholar 

  70. Khuth ST, Akaoka H, Pagenstecher A, Verlaeten O, Belin MF, Giraudon P, Bernard A (2001) Morbillivirus infection of the mouse central nervous system induces region-specific upregulation of MMPs and TIMPs correlated to inflammatory cytokine expression. J Virol 75: 8268–8282

    PubMed  CAS  Google Scholar 

  71. Szklarczyk A, Lapinska J, Rylski M, McKay RD, Kaczmarek L (2002) Matrix metalloproteinase-9 undergoes expression and activation during dendritic remodeling in adult hippocampus. J Neurosci 22: 920–930

    PubMed  CAS  Google Scholar 

  72. 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 

  73. Zagulska-Szymczak S, Filipkowski RK, Kaczmarek L (2001) Kainate-induced genes in the hippocampus: lessons from expression patterns. Neurochem Int 38: 485–501

    PubMed  CAS  Google Scholar 

  74. Jaworowicz DJ, Korytko PJ, Singh Lakhman S, Boje KM (1998) Nitric oxide and prostaglandin E2 formation parallels blood-brain barrier disruption in an experimental rat model of bacterial meningitis. Brain Res Bull 46: 541–546

    PubMed  CAS  Google Scholar 

  75. Nedivi E, Hevroni D, Naot D, Israeli D, Citri Y (1993) Numerous candidate plasticityrelated genes revealed by differential cDNA cloning. Nature 363: 718–722

    PubMed  CAS  Google Scholar 

  76. Schönbeck U, Mach F, Liby P (1998) Generation of biologically active IL-1β by matrix metalloproteinases: a novel caspase-1-independent pathway of IL-1β processing. J Immunol 161: 3340–3346

    PubMed  Google Scholar 

  77. Schwab S, Steiner T, Aschoff A, Schwarz S, Steiner HH, Jansen O, Hacke W (1998) Early hemicraniectomy in patients with complete middle cerebral artery infarction. Stroke 29: 1888–1893

    PubMed  CAS  Google Scholar 

  78. Clark WM, Albers GW, Madden KP, Hamilton S (2000) The rtPA (alteplase) 0-to 6-hour acute stroke trial, part A (A0276g): results of a double-blind, placebo-controlled, multicenter study. Thromblytic therapy in acute ischemic stroke study investigators. Stroke 31: 811–816

    PubMed  CAS  Google Scholar 

  79. Latour LL, Kang DW, Ezzeddine MA, Chalela JA, Warach S (2004) Early blood-brain barrier disruption in human focal brain ischemia. Ann Neurol 56: 468–477

    PubMed  Google Scholar 

  80. Neumann-Haefelin T, Kastrup A, de Crespigny A, Yenari MA, Ringer T, Sun GH, Moseley ME (2000) Serial MRI after transient focal cerebral ischemia in rats dynamics of tissue injury, blood-brain barrier damage, and edema formation. Stroke 31: 1965–1973

    PubMed  CAS  Google Scholar 

  81. Copin JC, Goodyear MC, Gidday JM, Shah AR, Morel DR, Gasche Y (2005) Role of matrix metalloproteinases in apoptosis following focal cerebral ischemia in rat and mice. Eur J Neurosci 22: 1597–1608

    PubMed  Google Scholar 

  82. Barone FC, Feuerstein GZ (1999) Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab 19: 819–834

    PubMed  CAS  Google Scholar 

  83. Petty MA, Wettstein JG (2001) Elements of cerebral microvascular ischaemia. Brain Res Brain Res Rev 36: 23–34

    PubMed  CAS  Google Scholar 

  84. Clark WM, Lutsep HL (2001) Potential of anticytokine therapies in central nervous system ischaemia. Expert Opin Biol Ther 1: 227–237

    PubMed  CAS  Google Scholar 

  85. Hosomi N, Ban CR, Naya T, Takahashi T, Guo P, Song XY, Kohno M (2005) Tumor necrosis factor-alpha neutralization reduced cerebral edema through inhibition of matrix metalloproteinase production after transient focal cerebral ischemia. J Cereb Blood Flow Metab 25: 959–967

    PubMed  CAS  Google Scholar 

  86. del Zoppo GJ (1994) Microvascular changes during cerebral ischemia and reperfusion. Cerebrovasc Brain Metab Rev 6: 47–96

    PubMed  Google Scholar 

  87. Okada Y, Copeland BR, Mori E (1994) P-selectin and intercellular adhesion molecule-1 expression after focal brain ischemia and reperfusion. Stroke 25: 202–211

    PubMed  CAS  Google Scholar 

  88. Yurchenco PD, Schittny JC (1990) Molecular architecture of basement membranes. FASEB J 4: 1577–1590

    PubMed  CAS  Google Scholar 

  89. Brooks PC, Montgomery AM, Rosenfeld M, Reisfeld RA, Hu T, Klier G, Cheresh DA (1994) Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79: 1157–1164

    PubMed  CAS  Google Scholar 

  90. Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE (1997) Geometric control of cell life and death. Science 276: 1425–1428

    PubMed  CAS  Google Scholar 

  91. Ingber DE, Folkman J (1989) How does extracellular matrix control capillary morphogenesis. Cell 58: 803–805

    PubMed  CAS  Google Scholar 

  92. Maniotis AJ, Chen CS, Ingber DE (1997) Demonstration of mechanical connections between integrins cytoskeletal filaments and nucleoplasm that stabilize nuclear structure. Proc Natl Acad Sci 94: 849–854

    PubMed  CAS  Google Scholar 

  93. Hamann GF, Okada Y, Fitridge R, Del Zoppo GJ (1995) Microvascular basal lamina antigens disappear during cerebral ischemia and reperfusion. Stroke 26: 2120–2126

    PubMed  CAS  Google Scholar 

  94. Belayev L, Busto R, Zhao W, Ginsberg MD (1996) Quantitative evaluation of bloodbrain barrier permeability following middle cerebral artery occlusion in rats. Brain Res 739: 88–96

    PubMed  CAS  Google Scholar 

  95. Kondo T, Reaume AG, Huang TT, Carlson E, Murakami K, Chen SF, Hoffman EK, Scott RW, Epstein CJ, Chan PH (1997) Reduction of CuZn-superoxide dismutase activity exacerbates neuronal cell injury and edema formation after transient focal cerebral ischemia. J Neurosci 17: 4180–4189

    PubMed  CAS  Google Scholar 

  96. Hamann GF, del Zoppo GJ, von Kummer R (1999) Hemorrhagic transformation of cerebral infarction-possible mechanisms. Thromb Haemost 82: 92–94

    PubMed  Google Scholar 

  97. Hamann GF, Okada Y, Del Zoppo GJ (1996) Hemorrhagic transformation and microvascular integrity during focal cerebral ischemi/reperfusion. J Cereb Blood Flow Metab 16: 1373–1378

    PubMed  CAS  Google Scholar 

  98. 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 

  99. Asahi M, Sumii T, Fini ME, Itohara S, Lo EH (2001) Matrix metalloproteinase 2 gene knockout has no effect on acute brain injury after focal ischemia. Neuroreport 12: 3003–3007

    PubMed  CAS  Google Scholar 

  100. Fukuda S, Fini CA, Mabuchi T, Koziol JA, Eggleston LL Jr, del Zoppo GJ (2004) Focal cerebral ischemia induces active proteases that degrade microvascular matrix. Stroke 35: 998–1004

    PubMed  CAS  Google Scholar 

  101. Yang YI, Estrada EY, Thompson JF, Liu W, Rosenberg GA (2007) Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat. J Cereb Blood Flow Metab 27: 697–709

    PubMed  CAS  Google Scholar 

  102. Opdenakker G, Van den Steen PE, Dubois B, Nelissen I, Van Coillie E, Masure S, Proost P, Van Damme J (2001) Gelatinase B functions as regulator and effector in leukocyte biology. J Leukoc Biol 69: 851–859

    PubMed  CAS  Google Scholar 

  103. Asahi M, Asahi K, Wang X, Lo EH (2000) Reduction of tissue plasminogen activatorinduced hemorrhage and brain injury by free radical spin trapping after embolic focal cerebral ischemia in rats. J Cereb Blood Flow Metab 20: 452–457

    PubMed  CAS  Google Scholar 

  104. Gursoy-Ozdemir Y, Can A, Dalkara T (2004) Reperfusion-induced oxidative/nitrative injury to neurovascular unit after focal cerebral ischemia. Stroke 35: 1449–1453

    PubMed  Google Scholar 

  105. Lewen A, Sugawara T, Gasche Y, Fujimura M, Chan PH (2001) Oxidative cellular damage and the reduction of APE/Ref-1 expression after experimental traumatic brain injury. Neurobiol Dis 8: 380–390

    PubMed  CAS  Google Scholar 

  106. Maier CM, Hsieh L, Crandall T, Narasimhan P, Chan PH (2006) Evaluating therapeutic targets for reperfusion-related brain hemorrhage. Ann Neurol 59: 929–938

    PubMed  CAS  Google Scholar 

  107. Lapchak PA, Chapman DF, Zivin JA (2000) Metalloproteinase inhibition reduces thrombolytic (tissue plasminogen activator)-induced hemorrhage after thromboembolic stroke. Stroke 31: 3034–3040

    PubMed  CAS  Google Scholar 

  108. Pfefferkorn T, Rosenberg GA (2003) Closure of the blood-brain barrier by matrix metalloproteinase inhibition reduces rtPA-mediated mortality in cerebral ischemia with delayed reperfusion. Stroke 34: 2025–2030

    PubMed  Google Scholar 

  109. Zhang RL, Chopp M, Zhang ZG, Jiang Q, Ewing JR (1997) A rat model of focal embolic cerebral ischemia. Brain Res 766: 83–92

    PubMed  CAS  Google Scholar 

  110. Wang CX, Yang T, Shuaib A (2001) An improved version of embolic model of brain ischemic injury in the rat. J Neurosci Methods 109: 147–151

    PubMed  CAS  Google Scholar 

  111. Sumii T, Lo EH (2002) Involvement of matrix metalloproteinase in thrombolysisassociated hemorrhagic transformation after embolic focal ischemia in rats. Stroke 33: 831–836

    PubMed  CAS  Google Scholar 

  112. Wang X, Lee SR, Arai K, Lee SR, Tsuji K, Rebeck GW, Lo EH (2003) Lipoprotein receptor-mediated induction of matrix metalloproteinase by tissue plasminogen activator. Nat Med 9: 1313–1317

    PubMed  CAS  Google Scholar 

  113. Yepes M, Sandkvist M, Moore EG, Bugge TH, Strickland DK, Lawrence DA (2003) Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein. J Clin Invest 112: 1533–1540

    PubMed  CAS  Google Scholar 

  114. Wang J, Tsirka SE (2005) Neuroprotection by inhibition of matrix metalloproteinases in a mouse model of intracerebral haemorrhage. Brain 128: 1622–1633

    PubMed  Google Scholar 

  115. Svedin P, Hagberg H, Sävman K, Zhu C, Mallard C (2007) Matrix metalloproteinase-9 gene knock-out protects the immature brain after cerebral hypoxia-ischemia. J Neurosci 27: 1511–1518

    PubMed  CAS  Google Scholar 

  116. Montaner J, Molina CA, Monasterio J, Abilleira S, Arenillas JF, Ribo M, Quintana M, Alvarez-Sabin J (2003) Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke. Circulation 107: 598–603

    PubMed  CAS  Google Scholar 

  117. Castellanos M, Sobrino T, Millan M, Garcia M, Arenillas J, Nombela F, Brea D, Perez de la Ossa N, Serena J, Vivancos J et al (2007) Serum cellular fibronectin and matrix metalloproteinase-9 as screening biomarkers for the prediction of parenchymal hematoma after thrombolytic therapy in acute ischemic stroke. A multicenter confirmatory study. Stroke 38: 1855–1859

    PubMed  CAS  Google Scholar 

  118. Montaner J, Alvarez-Sabin J, Molina C, Angles A, Abilleira S, Arenillas J, Gonzalez MA, Monasterio J (2001) Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment. Stroke 32: 1759–1766

    PubMed  CAS  Google Scholar 

  119. Montaner J, Alvarez-Sabin J, Molina CA, Angles A, Abilleira S, Arenillas J, Monasterio J (2001) Matrix metalloproteinase expression is related to hemorrhagic transformation after cardioembolic stroke. Stroke 32: 2762–2767

    PubMed  CAS  Google Scholar 

  120. Backstrom JR, Lim GP, Cullen MJ, Tokes ZA (1996) Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons of the human hippocampus and is capable of degrading the amyloid-beta peptide (1-40). J Neurosci 16: 7910–7919

    PubMed  CAS  Google Scholar 

  121. Massengale JL, Gasche Y, Chan PH (2002) Carbohydrate source influences gelatinase production by mouse astrocytes in vitro. Glia 38: 240–245

    PubMed  Google Scholar 

  122. Gottschall PE, Yu X, Bing B (1995) Increased production of gelatinase B (matrix metalloproteinase-9) and interleukin-6 by activated rat microglia in culture. J Neurosci Res 42: 335–342

    PubMed  CAS  Google Scholar 

  123. Oh LY, Larsen PH, Krekoski CA, Edwards DR, Donovan F, Werb Z, Yong VW (1999) Matrix metalloproteinase-9/gelatinase B is required for process outgrowth by oligodendrocytes. J Neurosci 19: 8464–8475

    PubMed  CAS  Google Scholar 

  124. Investigators EAST (2001) Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial. Neurology 57: 1428–1434

    Google Scholar 

  125. Furuya K, Takeda H, Azhar S, McCarron RM, Chen Y, Ruetzler CA, Wolcott KM, DeGraba TJ, Rothlein R, Hugli TE et al (2001) Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine antihuman intercellular adhesion molecule-1 antibody: a bedside-to-bench study. Stroke 32: 2665–2674

    PubMed  CAS  Google Scholar 

  126. Gursoy-Ozdemir Y, Qiu J, Matsuoka N, Bolay H, Bermpohl D, Jin H, Wang X, Rosenberg GA, Lo EH, Moskowitz MA (2004) Cortical spreading depression activates and upregulates MMP-9. J Clin Invest 113: 1447–1455

    PubMed  CAS  Google Scholar 

  127. Ferri KF, Kroemer G (2001) Organelle-specific initiation of cell death pathways. Nat Cell Biol 3: E255–263

    PubMed  CAS  Google Scholar 

  128. Ferri KF, Kroemer G (2001) Mitochondria-the suicide organelles. Bioessays 23: 111–115

    PubMed  CAS  Google Scholar 

  129. Wang H, Yu SW, Koh DW, Lew J, Coombs C, Bowers W, Federoff HJ, Poirier GG, Dawson TM, Dawson VL (2004) Apoptosis-inducing factor substitutes for caspase executioners in NMDA-triggered excitotoxic neuronal death. J Neurosci 24: 10963–10973

    PubMed  CAS  Google Scholar 

  130. Yu SW, Wang H, Dawson TM, Dawson VL (2003) Poly(ADP-ribose) polymerase-1 and apoptosis inducing factor in neurotoxicity. Neurobiol Dis 14: 303–317

    PubMed  CAS  Google Scholar 

  131. Plesnila N, Zinkel S, Le DA, Amin-Hanjani S, Wu Y, Qiu J, Chiarugi A, Thomas SS, Kohane DS, Korsmeyer SJ et al (2001) BID mediates neuronal cell death after oxygen/glucose deprivation and focal cerebral ischemia. Proc Natl Acad Sci USA 98: 15318–15323

    PubMed  CAS  Google Scholar 

  132. Wallach D, Varfolomeev EE, Malinin NL, Goltsev YV, Kovalenko AV, Boldin MP (1999) Tumor necrosis factor receptor and Fas signaling mechanisms. Annu Rev Immunol 17: 331–367

    PubMed  CAS  Google Scholar 

  133. Vogelstein B, Lane D, Levine AJ (2000) Surfing the p53 network. Nature 408: 307–310

    PubMed  CAS  Google Scholar 

  134. Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79: 1431–1568

    PubMed  CAS  Google Scholar 

  135. Hara H, Friedlander RM, Gagliardini V, Ayata C, Fink K, Huang Z, Shimizu-Sasamata M, Yuan J, Moskowitz MA (1997) Inhibition of interleukin 1beta converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage. Proc Natl Acad Sci USA 94: 2007–2012

    PubMed  CAS  Google Scholar 

  136. Sugawara T, Noshita N, Lewen A, Gasche Y, Ferrand-Drake M, Fujimura M, Morita-Fujimura Y, Chan PH (2002) Overexpression of copper/zinc superoxide dismutase in transgenic rats protects vulnerable neurons against ischemic damage by blocking the mitochondrial pathway of caspase activation. J Neurosci 22: 209–217

    PubMed  CAS  Google Scholar 

  137. Jourquin J, Tremblay E, Decanis N, Charton G, Hanessian S, Chollet AM, Le Diguardher T, Khrestchatisky M, Rivera S (2003) Neuronal activity-dependent increase of net matrix metalloproteinase activity is associated with MMP-9 neurotoxicity after kainate. Eur J Neurosci 18: 1507–1517

    PubMed  Google Scholar 

  138. Lee SR, Tsuji K, Lee SR, Lo EH (2004) Role of matrix metalloproteinases in delayed neuronal damage after transient global cerebral ischemia. J Neurosci 24: 671–678

    PubMed  CAS  Google Scholar 

  139. Tan HK, Heywood D, Ralph GS, Bienemann A, Baker AH, Uney JB (2003) Tissue inhibitor of metalloproteinase 1 inhibits excitotoxic cell death in neurons. Mol Cell Neurosci 22: 98–106

    PubMed  CAS  Google Scholar 

  140. Wallace JA, Alexander S, Estrada EY, Hines C, Cunningham LA, Rosenberg GA (2002) Tissue inhibitor of metalloproteinase-3 is associated with neuronal death in reperfusion injury. J Cereb Blood Flow Metab 22: 1303–1310

    PubMed  CAS  Google Scholar 

  141. Wetzel M, Rosenberg GA, Cunningham LA (2003) Tissue inhibitor of metalloproteinases-3 and matrix metalloproteinase-3 regulate neuronal sensitivity to doxorubicininduced apoptosis. Eur J Neurosci 18: 1050–1060

    PubMed  CAS  Google Scholar 

  142. Fawcett JW, Asher RA (1999) The glial scar and central nervous system repair. Brain Res Bull 49: 377–391

    PubMed  CAS  Google Scholar 

  143. Ridet JL, Malhotra SK, Privat A, Gage FH (1997) Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci 20: 570–577

    PubMed  CAS  Google Scholar 

  144. Levine JM, Reynolds R, Fawcett JW (2001) The oligodendrocyte precursor cell in health and disease. Trends Neurosci 24: 39–47

    PubMed  CAS  Google Scholar 

  145. Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19: 312–318

    PubMed  CAS  Google Scholar 

  146. McGraw J, Hiebert GW, Steeves JD (2001) Modulating astrogliosis after neurotrauma. J Neurosci Res 63: 109–115

    PubMed  CAS  Google Scholar 

  147. Campbell IL, Pagenstecher A (1999) Matrix metalloproteinases and their inhibitors in the nervous system: the good, the bad and the enigmatic. Trends Neurosci 22: 285–287

    PubMed  CAS  Google Scholar 

  148. Murphy G, Gavrilovic J (1999) Proteolysis and cell migration: creating a path? Curr Opin Cell Biol 11: 614–621

    PubMed  CAS  Google Scholar 

  149. Ferguson TA, Muir D (2000) MMP-2 and MMP-9 increase the neurite-promoting potential of schwann cell basal laminae and are upregulated in degenerated nerve. Mol Cell Neurosci 16: 157–167

    PubMed  CAS  Google Scholar 

  150. Duchossoy Y, Horvat JC, Stettler O (2001) MMP-related gelatinase activity is strongly induced in scar tissue of injured adult spinal cord and forms pathways for ingrowing neurites. Mol Cell Neurosci 17: 945–956

    PubMed  CAS  Google Scholar 

  151. Ellison JA, Velier JJ, Spera P, Jonak ZL, Wang X, Barone FC, Feuerstein GZ (1998) Osteopontin and its integrin receptor alpha(v)beta3 are upregulated during formation of the glial scar after focal stroke. Stroke 29: 1698–1706; discussion 1707

    PubMed  CAS  Google Scholar 

  152. Agnihotri R, Crawford HC, Haro H, Matrisian LM, Havrda MC, Liaw L (2001) Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin). J Biol Chem 276: 28261–28267

    PubMed  CAS  Google Scholar 

  153. Copin JC, Gasche Y (2007) Matrix metalloproteinase-9 deficiency has no effect on glial scar formation after transient focal cerebral ischemia in mouse. Brain Res 1150: 167–173

    PubMed  CAS  Google Scholar 

  154. Zhao BQ, Wang S, Kim HY, Storrie H, Rosen BR, Mooney DJ, Wang X, Lo EH (2006) Role of matrix metalloproteinases in delayed cortical responses after stroke. Nat Med 12: 441–445

    PubMed  CAS  Google Scholar 

  155. Sood RR, Taheri S, Candelario-Jalil E, Estrada EY, Rosenberg GA (2008) Early beneficial effect of matrix metalloproteinase inhibition on blood-brain barrier permeability as measured by magnetic resonance imaging countered by impaired long-term recovery after stroke in rat brain. J Cereb Blood Flow Metab 28: 431–438

    PubMed  CAS  Google Scholar 

  156. Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, Anca-Hershkowitz M, Sadeh M (2007) Minocycline treatment in acute stroke: An open-label, evaluatorblinded study. Neurology 69: 1404–1410

    PubMed  CAS  Google Scholar 

  157. Koistinaho M, Malm TM, Kettunen MI, Goldsteins G, Starckx S, Kauppinen RA, Opdenakker G, Koistinaho J (2005) Minocycline protects against permanent cerebral ischemia in wild type but not in matrix metalloprotease-9-deficient mice. J Cereb Blood Flow Metab 25: 460–467

    PubMed  CAS  Google Scholar 

  158. Jordan J, Fernandez-Gomez FJ, Ramos M, Ikuta I, Aguirre N, Galindo MF (2007) Minocycline and cytoprotection: shedding new light on a shadowy controversy. Current Drug Delivery 4: 225–231

    PubMed  CAS  Google Scholar 

  159. Wasserman JK, Schlichter LC (2007) Minocycline protects the blood-brain barrier and reduces intracerebral hemorrhage in the rat. Experimental Neurol 207: 227–237

    CAS  Google Scholar 

  160. Matyszak MK, Perry VH (1996) Delayed-type hypersensitivity lesions in the central nervous system are prevented by inhibitors of matrix metalloproteinases. J Neuroimmunol 69: 141–149

    PubMed  CAS  Google Scholar 

  161. Chandler S, Miller KM, Clements JM, Lury J, Corkill D, Anthony DC, Adams SE, Gearing AJ (1997) Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview. J Neuroimmunol 72: 155–161

    PubMed  CAS  Google Scholar 

  162. Opdenakker G, Van Damme J (1994) Cytokine-regulated proteases in autoimmune diseases. Immunol Today 15: 103–107

    PubMed  CAS  Google Scholar 

  163. Dubois B, Masure S, Hurtenbach U, Paemen L, Heremans H, van den Oord J, Sciot R, Meinhardt T, Hammerling G, Opdenakker G et al (1999) Resistance of young gelatinase B-deficient mice to experimental autoimmune encephalomyelitis and necrotizing tail lesions. J Clin Invest 104: 1507–1515

    PubMed  CAS  Google Scholar 

  164. Lou J, Gasche Y, Zheng L, Giroud C, Morel P, Clements J, Ythier A, Grau GE (1999) Interferon-beta inhibits activated leukocyte migration through human brain microvascular endothelial cell monolayer. Lab Invest 79: 1015–1025

    PubMed  CAS  Google Scholar 

  165. Leppert D, Waubant E, Burk MR, Oksenberg JR, Hauser SL (1996) Interferon beta-1b inhibits gelatinase secretion and in vitro migration of human T cells: a possible mechanism for treatment efficacy in multiple sclerosis. Ann Neurol 40: 846–852

    PubMed  CAS  Google Scholar 

  166. Stuve O, Dooley NP, Uhm JH, Antel JP, Francis GS, Williams G, Yong VW (1996) Interferon beta-1b decreases the migration of T lymphocytes in vitro: effects on matrix metalloproteinase-9. Ann Neurol 40: 853–863

    PubMed  CAS  Google Scholar 

  167. Ozenci V, Kouwenhoven M, Teleshova N, Pashenkov M, Fredrikson S, Link H (2000) Multiple sclerosis: pro-and anti-inflammatory cytokines and metalloproteinases are affected differentially by treatment with IFN-beta. J Neuroimmunol 108: 236–243

    PubMed  CAS  Google Scholar 

  168. Nelissen I, Martens E, Van den Steen PE, Proost P, Ronsse I, Opdenakker G (2003) Gelatinase B/matrix metalloproteinase-9 cleaves interferon-beta and is a target for immunotherapy. Brain 126: 1371–1381

    PubMed  Google Scholar 

  169. Shipley JM, Wesselschmidt RL, Kobayashi DK, Ley TJ, Shapiro SD (1996) Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice. Proc Natl Acad Sci USA 93: 3942–3946

    PubMed  CAS  Google Scholar 

  170. Durand ML, Calderwood SB, Weber DJ, Miller SI, Southwick FS, Caviness VS Jr, Swartz MN (1993) Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med 328: 21–28

    PubMed  CAS  Google Scholar 

  171. Kastenbauer S, Pfister HW (2003) Pneumococcal meningitis in adults: spectrum of complications and prognostic factors in a series of 87 cases. Brain 126: 1015–1025

    PubMed  Google Scholar 

  172. Pfister HW, Borasio GD, Dirnagl U, Bauer M, Einhaupl KM (1992) Cerebrovascular complications of bacterial meningitis in adults. Neurology 42: 1497–1504

    PubMed  CAS  Google Scholar 

  173. Pfister HW, Feiden W, Einhaupl KM (1993) Spectrum of complications during bacterial meningitis in adults. Results of a prospective clinical study. Arch Neurol 50: 575–581

    PubMed  CAS  Google Scholar 

  174. van de Beek D, de Gans J, McIntyre P, Prasad K (2004) Steroids in adults with acute bacterial meningitis: a systematic review. Lancet Infect Dis 4: 139–143

    PubMed  Google Scholar 

  175. Tauber MG, Moser B (1999) Cytokines and chemokines in meningeal inflammation: biology and clinical implications. Clin Infect Dis 28: 1–11; quiz 12

    PubMed  CAS  Google Scholar 

  176. Leib SL, Tauber MG (1999) Pathogenesis of bacterial meningitis. Infect Dis Clin North Am 13: 527–548, v–vi

    PubMed  CAS  Google Scholar 

  177. Meli DN, Christen S, Leib SL (2003) Matrix metalloproteinase-9 in pneumococcal meningitis: activation via an oxidative pathway. J Infect Dis 187: 1411–1415

    PubMed  CAS  Google Scholar 

  178. Meli DN, Loeffler JM, Baumann P, Neumann U, Buhl T, Leppert D, Leib SL (2004) In pneumococcal meningitis a novel water-soluble inhibitor of matrix metalloproteinases and TNF-alpha converting enzyme attenuates seizures and injury of the cerebral cortex. J Neuroimmunol 151: 6–11

    PubMed  CAS  Google Scholar 

  179. Nau R, Bruck W (2002) Neuronal injury in bacterial meningitis: mechanisms and implications for therapy. Trends Neurosci 25: 38–45

    PubMed  CAS  Google Scholar 

  180. Nau R, Wellmer A, Soto A, Koch K, Schneider O, Schmidt H, Gerber J, Michel U, Bruck W (1999) Rifampin reduces early mortality in experimental Streptococcus pneumoniae meningitis. J Infect Dis 179: 1557–1560

    PubMed  CAS  Google Scholar 

  181. Williams PL, Leib SL, Kamberi P, Leppert D, Sobel RA, Bifrare YD, Clemons KV, Stevens DA (2002) Levels of matrix metalloproteinase-9 within cerebrospinal fluid in a rabbit model of coccidioidal meningitis and vasculitis. J Infect Dis 186: 1692–1695

    PubMed  CAS  Google Scholar 

  182. Bottcher T, Spreer A, Azeh I, Nau R, Gerber J (2003) Matrix metalloproteinase-9 deficiency impairs host defense mechanisms against Streptococcus pneumoniae in a mouse model of bacterial meningitis. Neurosci Lett 338: 201–204

    PubMed  CAS  Google Scholar 

  183. Kim GW, Gasche Y, Grzeschik S, Copin JC, Maier CM, Chan PH (2003) Neurodegeneration in striatum induced by the mitochondrial toxin 3-nitropropionic acid: role of matrix metalloproteinase-9 in early blood-brain barrier disruption? J Neurosci 23: 8733–8742

    PubMed  CAS  Google Scholar 

  184. Nakada M, Okada Y, Yamashita J (2003) The role of matrix metalloproteinases in glioma invasion. Front Biosci 8: e261–269

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Pharmacology and Intensive Care, Geneva University Hospitals and Geneva Neuroscience Center, University of Geneva, 1211, Geneva, Switzerland

    Yvan Gasche & Jean-Christophe Copin

Authors
  1. Yvan Gasche
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jean-Christophe Copin
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. INSERM U620 Faculté des Sciences Pharmaceutiques et Biologique, Université de Rennes 1, Avenue du Professeur Léon Bernard 2, 35043, Rennes CX, France

    Vincent Lagente  & Elisabeth Boichot  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Gasche, Y., Copin, JC. (2008). Matrix metalloproteinases and inflammatory diseases of the central nervous system. In: Lagente, V., Boichot, E. (eds) Matrix Metalloproteinases in Tissue Remodelling and Inflammation. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8585-9_8

Download citation

Publish with us

Policies and ethics

Search

Navigation