Immunohistochemical profile of NF-κB/p50, NF-κB/p65, MMP-9, MMP-2, and u-PA in experimental cervical spondylotic myelopathy.
METHODS
The immunohistochemical profile of nuclear factor-κ B (NF-κB)/p50, NF-κB/p65, matrix metalloproteinase (MMP)-9, MMP-2, and urokinase-type plasminogen activator (u-PA) proteins was examined in spinal cord tissues coming from rabbits, which underwent chronic cervical spinal cord compression.


OBJECTIVE
To study the potential role of NF-κB and extracellular matrix proteins under the chronic mechanical compression of the cervical spinal cord.


BACKGROUND
Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction among adults older than 55 years. Neuronal loss, myelin destruction, axonal degeneration, and glial scar formation are the principal neuropathological features of CSM. However, the biologic pathways that lead to these features remain unclear.


METHODS
In this study, we used a new animal experimental model of CSM developed in our laboratory. Briefly, after posterior cervical laminectomy, gradual and progressive compression (during 20 weeks) was achieved by introducing a piece of aromatic polyether (0.07 mm thick) under the C6 lamina in 15 New Zealand rabbits. In control animals (n = 15), the aromatic polyether was implanted and then removed after 60 seconds (sham operation). The immunoreactivity of p50 and p65 subunits of NF-kB, as well as that of MMP-2, MMP-9, and u-PA, was evaluated in paraffin-embedded spinal cord sections coming from both groups. The evaluation was performed using immunohistochemistry technique and the results were analyzed using SPSS for Windows, release 12.0 (SPSS Inc., Chicago, IL).


RESULTS
Increased immunoreactivity of both NF-κB subunits, p50 and p65, as well as MMP-2, MMP-9, and u-PA was demonstrated in animals with CSM in comparison with controls. Statistical analysis of the results revealed strong positive correlation between NF-κB subunits immunoreactivity and that of MMP-9, MMP-2, and u-PA.


CONCLUSIONS
There is a strong correlation between the immunoexpression of NF-κB/p50, NF-κB/p65, MMP-2, MMP-9, u-PA, and CSM.
Department of Neurosurgery, University Hospital of Patras, Rio Patras, Greece. karadimas_spyros@yahoo.com
Spyridon K
SK
Karadimas
George
G
Klironomos
Dionysios J
DJ
Papachristou
Sofia
S
Papanikolaou
Eleni
E
Papadaki
George
G
Gatzounis
D000818:Animals; D002574:Cervical Vertebrae / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000096:biosynthesis*; D052002:NF-kappa B p50 Subunit / Q000032:analysis / Q000096:biosynthesis*; D011817:Rabbits; D013118:Spinal Cord Diseases / Q000378:metabolism / Q000473:pathology; D055009:Spondylosis / Q000378:metabolism* / Q000473:pathology; D051996:Transcription Factor RelA / Q000032:analysis / Q000096:biosynthesis*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000096:biosynthesis*
D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9