QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (88) Citing Articles via Google Scholar Google Scholar Articles by Noble, L. J. Articles by Werb, Z. Search for Related Content PubMed PubMed Citation Articles by Noble, L. J. Articles by Werb, Z.

 Previous Article  |  Next Article 

The Journal of Neuroscience, September 1, 2002, 22(17):7526-7535

Matrix Metalloproteinases Limit Functional Recovery after Spinal Cord Injury by Modulation of Early Vascular Events

Linda J. Noble¹, Frances Donovan², Takuji Igarashi¹, Staci Goussev¹, and Zena Werb²

Departments of ¹ Neurosurgery and ² Anatomy, University of California at San Francisco, San Francisco, California 94143-0520

Inflammation in general and proteinases generated as a result are likely mediators of early secondary pathogenesis after spinal cord injury. We report that matrix metalloproteinase-9 (MMP-9) plays an important role in blood-spinal cord barrier dysfunction, inflammation, and locomotor recovery. MMP-9 was present in the meninges and neurons of the uninjured cord. MMP-9 increased rapidly after a moderate contusion spinal cord injury, reaching a maximum at 24 hr, becoming markedly reduced by 72 hr, and not detectable at 7 d after injury. It was seen in glia, macrophages, neutrophils, and vascular elements in the injured spinal cord at 24 hr after injury. The natural tissue inhibitors of MMPs were unchanged over this time course. MMP-9-null mice exhibited significantly less disruption of the blood-spinal cord barrier, attenuation of neutrophil infiltration, and significant locomotor recovery compared with wild-type mice. Similar findings were observed in mice treated with a hydroxamic acid MMP inhibitor from 3 hr to 3 d after injury, compared with the vehicle controls. Moreover, the area of residual white matter at the lesion epicenter was significantly greater in the inhibitor-treated group. This study provides evidence that MMP-9 plays a key role in abnormal vascular permeability and inflammation within the first 3 d after spinal cord injury, and that blockade of MMPs during this critical period attenuates these vascular events and leads to improved locomotor recovery. Our findings suggest that early inhibition of MMPs may be an efficacious strategy for the spinal cord-injured patient.

Key words: blood-spinal cord barrier; inflammation; locomotor recovery; matrix metalloproteinase-9; proteinases; spinal cord injury

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/22177526-10$05.00/0

This article has been cited by other articles:

				S. A. Busch, K. P. Horn, D. J. Silver, and J. Silver Overcoming Macrophage-Mediated Axonal Dieback Following CNS Injury J. Neurosci., August 12, 2009; 29(32): 9967 - 9976. [Abstract] [Full Text] [PDF]

				J.-Y. C. Hsu, L. Y. W. Bourguignon, C. M. Adams, K. Peyrollier, H. Zhang, T. Fandel, C. L. Cun, Z. Werb, and L. J. Noble-Haeusslein Matrix Metalloproteinase-9 Facilitates Glial Scar Formation in the Injured Spinal Cord J. Neurosci., December 10, 2008; 28(50): 13467 - 13477. [Abstract] [Full Text] [PDF]

				A. Szklarczyk, O. Ewaleifoh, J.-C. Beique, Y. Wang, D. Knorr, N. Haughey, T. Malpica, M. P. Mattson, R. Huganir, and K. Conant MMP-7 cleaves the NR1 NMDA receptor subunit and modifies NMDA receptor function FASEB J, November 1, 2008; 22(11): 3757 - 3767. [Abstract] [Full Text] [PDF]

				M. Hashimoto, D. Sun, S. R. Rittling, D. T. Denhardt, and W. Young Osteopontin-Deficient Mice Exhibit Less Inflammation, Greater Tissue Damage, and Impaired Locomotor Recovery from Spinal Cord Injury Compared with Wild-Type Controls J. Neurosci., March 28, 2007; 27(13): 3603 - 3611. [Abstract] [Full Text] [PDF]

				J. C. Fleming, M. D. Norenberg, D. A. Ramsay, G. A. Dekaban, A. E. Marcillo, A. D. Saenz, M. Pasquale-Styles, W. D. Dietrich, and L. C. Weaver The cellular inflammatory response in human spinal cords after injury Brain, December 1, 2006; 129(12): 3249 - 3269. [Abstract] [Full Text] [PDF]

				J.-Y. C. Hsu, R. McKeon, S. Goussev, Z. Werb, J.-U. Lee, A. Trivedi, and L. J. Noble-Haeusslein Matrix Metalloproteinase-2 Facilitates Wound Healing Events That Promote Functional Recovery after Spinal Cord Injury J. Neurosci., September 27, 2006; 26(39): 9841 - 9850. [Abstract] [Full Text] [PDF]

				F. Qiao, C. Atkinson, H. Song, R. Pannu, I. Singh, and S. Tomlinson Complement Plays an Important Role in Spinal Cord Injury and Represents a Therapeutic Target for Improving Recovery following Trauma Am. J. Pathol., September 1, 2006; 169(3): 1039 - 1047. [Abstract] [Full Text] [PDF]

				M. L. Lindsey, G. P. Escobar, L. W. Dobrucki, D. K. Goshorn, S. Bouges, J. T. Mingoia, D. M. McClister Jr., H. Su, J. Gannon, C. MacGillivray, et al. Matrix metalloproteinase-9 gene deletion facilitates angiogenesis after myocardial infarction Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H232 - H239. [Abstract] [Full Text] [PDF]

				A. Gorio, L. Madaschi, B. Di Stefano, S. Carelli, A. M. Di Giulio, S. De Biasi, T. Coleman, A. Cerami, and M. Brines From The Cover: Methylprednisolone neutralizes the beneficial effects of erythropoietin in experimental spinal cord injury PNAS, November 8, 2005; 102(45): 16379 - 16384. [Abstract] [Full Text] [PDF]

				E. D. Shwartz MRI and the Evaluation of the Blood-Spinal Cord Barrier following Injury AJNR Am. J. Neuroradiol., August 1, 2005; 26(7): 1609 - 1610. [Full Text] [PDF]

				T. M. Kauppinen and R. A. Swanson Poly(ADP-Ribose) Polymerase-1 Promotes Microglial Activation, Proliferation, and Matrix Metalloproteinase-9-Mediated Neuron Death J. Immunol., February 15, 2005; 174(4): 2288 - 2296. [Abstract] [Full Text] [PDF]

				M. J. Velardo, C. Burger, P. R. Williams, H. V. Baker, M. C. Lopez, T. H. Mareci, T. E. White, N. Muzyczka, and P. J. Reier Patterns of Gene Expression Reveal a Temporally Orchestrated Wound Healing Response in the Injured Spinal Cord J. Neurosci., September 29, 2004; 24(39): 8562 - 8576. [Abstract] [Full Text] [PDF]

				P. H. Larsen, J. E. Wells, W. B. Stallcup, G. Opdenakker, and V. W. Yong Matrix Metalloproteinase-9 Facilitates Remyelination in Part by Processing the Inhibitory NG2 Proteoglycan J. Neurosci., December 3, 2003; 23(35): 11127 - 11135. [Abstract] [Full Text] [PDF]

				J. E. A. Wells, T. K. Rice, R. K. Nuttall, D. R. Edwards, H. Zekki, S. Rivest, and V. W. Yong An Adverse Role for Matrix Metalloproteinase 12 after Spinal Cord Injury in Mice J. Neurosci., November 5, 2003; 23(31): 10107 - 10115. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help