Molecular mechanisms of spinal cord dysfunction and cell death in the spinal hyperostotic mouse: Implications for the pathophysiology of human cervical spondylotic myelopathy

Autor: Wen-Ru Yu, Darryl C. Baptiste, Tianyi Liu, Ewa Odrobina, Greg J. Stanisz, Michael G. Fehlings
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Zdroj: Neurobiology of Disease, Vol 33, Iss 2, Pp 149-163 (2009)
Druh dokumentu: article
ISSN: 1095-953X
35567333
DOI: 10.1016/j.nbd.2008.09.024
Popis: Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction in adults in Western society. Paradoxically, relatively little is known about the pathobiological mechanisms associated with the progressive loss of neural tissue in the spinal cord of CSM patients. In this report we have utilized the twy/twy mutant mouse, which develops ossification of the ligamentum flavum at C2–C3 and exhibits progressive paralysis. This animal model represents an excellent in vivo model of CSM. This study reports novel evidence, which demonstrates that chronic extrinsic cervical spinal cord compression leads to Fas-mediated apoptosis of neurons and oligodendrocytes which is associated with activation of caspase-8, -9 and -3 and progressive neurological deficits. While surgical decompression will remain the mainstay of management of CSM, molecular therapies, which target Fas-mediated apoptosis could show promise as a complementary approach to maximize neurological recovery in this common spinal cord condition.
Databáze: Directory of Open Access Journals
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