Matrix metalloproteinases: potential therapeutic target in spinal cord injury.
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.
Duchossoy
Y
Y
Neurolab, Biological Research Laboratory, Paris, France.
Arnaud
S
S
Feldblum
S
S
D000818:Animals; D003288:Contusions / Q000188:drug therapy; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000627:therapeutic use; D020780:Matrix Metalloproteinase 9 / Q000627:therapeutic use; D020782:Matrix Metalloproteinases / Q000627:therapeutic use*; D009389:Neovascularization, Pathologic; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000201:enzymology*; D013997:Time Factors
D018093:Gelatinases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9