Duchossay, et al. (2001). Matrix metalloproteinases: potential therapeutic target in spinal cord injury

[Wise Young]

• Duchossoy Y, Arnaud S and Feldblum S (2001). Matrix metalloproteinases: potential therapeutic target in spinal cord injury. Clin Chem Lab Med. 39 (4): 362-7. Summary: Mediators of extracellular matrix proteins degradation, the matrix metalloproteinases (MMPs), involved in inflammation as well as facilitation of process outgrowth of oligodendrocytes are interesting targets for neural repair. Recent data reported their activation after seizures, cerebral ischemia and spinal cord injury. The present study was designed to localize at cellular level the gelatinase activity by in situ zymography in a rat spinal cord contusion model. The kinetic of gelatinase activation was monitored by in situ zymography on 20 microm cryostat sections. The fluorescein-quenched DQ gelatin digestion yielded cleaved fluorescent peptides enabling the detection of gelatinase activity at cellular level. Twenty four hours and 48 h after injury, a strong gelatinase activity was detected at the lesion site in and around vascular structures and infiltrated cells. A preincubation with either MMP-2 or MMP-9 antibodies significantly decreases the gelatinase activity pattern, suggesting the involvement of at least both MMPs. Our results are consistent with a role for MMPs in the blood spinal barrier disruption, the leukocytes infiltration, the disruption of the extracellular matrix and the clearance of debris. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&li st_uids=11388663> Neurolab, Biological Research Laboratory, Paris, France.

• Duchossoy Y, Horvat JC and 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 (6): 945-56. Summary: Scar formation following adult spinal cord (SC) hemisection is accompanied by important remodeling of the surrounding extracellular matrix (ECM). Since ECM molecules provide the substrate for axon growth, these changes in ECM composition are likely to influence the process of axonal regeneration. Here we investigated whether scar formation could be associated with the activation of matrix metalloproteinases (MMPs), a class of proteins implicated in ECM remodeling thought to favor axonal regeneration in the peripheral nervous system. Two members of the MMP family, MMP-2 and MMP-9, were found to be transiently upregulated in the SC wound. In situ fluorescent zymography revealed a MMP-related gelatinase activity (GA) in the wound, which was spatially and temporally correlated with scar formation. The GA formed a striking pattern of interwoven pathways along which neurites were seen to grow. These pathways corresponded to the distribution of other ECM molecules, which are known to have antagonistic effects on axonal regrowth. Our results suggest that neurite ingrowth into the wound may transiently benefit from this ECM remodeling and, in particular, from the upregulation of MMPs. Copyright 2001 Academic Press. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&li st_uids=11414785> Laboratoire de Neurobiologie, Universite Paris V Rene Descartes, Paris, France.