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01.03.2012 | Original Article | Ausgabe 3/2012 Open Access

European Spine Journal 3/2012

Apoptosis of neurons and oligodendrocytes in the spinal cord of spinal hyperostotic mouse (twy/twy): possible pathomechanism of human cervical compressive myelopathy

European Spine Journal > Ausgabe 3/2012
Kenzo Uchida, Hideaki Nakajima, Shuji Watanabe, Takafumi Yayama, Alexander Rodriguez Guerrero, Tomoo Inukai, Takayuki Hirai, Daisuke Sugita, William E. Johnson, Hisatoshi Baba
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s00586-011-2025-x) contains supplementary material, which is available to authorized users.



Cervical compressive myelopathy is the most serious complication of cervical spondylosis or ossification of the posterior longitudinal ligament (OPLL) and the most frequent cause of spinal cord dysfunction. There is little information on the exact pathophysiological mechanism responsible for the progressive loss of neural tissue in the spinal cord of such patients. In this study, we used the spinal hyperostotic mouse (twy/twy) as a suitable model of human spondylosis, and OPLL to investigate the cellular and molecular changes in the spinal cord. Mutant twy/twy mouse developed ossification of the ligamentum flavum at C2–C3 and exhibited progressive paralysis.

Materials and methods

The mutant twy/twy mice, aged 16 and 24 weeks, were used in the present study. The cervical spinal cord was analyzed histologically and immunohistochemically.


We observed that a significant correlation between the proportion of apoptotic oligodendrocytes in the compressed area of the spinal cord and the magnitude of cord compression. Immunohistochemical analysis indicated overexpression of TNFR1, CD95, and p75NTR in the twy/twy mice, which was localized by the immunofluorescence in the neurons and oligodendrocytes.


The expression of such factors seems to play at least some role in the apoptotic process, which probably contributes to axonal degeneration and demyelination in the twy/twy mice spinal cords with severe compression.

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