S. Casha et al., Oligodendroglial apoptosis occurs along degenerating axons and is associated with Fas and p75 expression following spinal cord injury in the rat, NEUROSCIENC, 103(1), 2001, pp. 203-218
Apoptosis or programmed cell death has been reported after CNS trauma. Howe
ver, the significance of this mechanism in the pathophysiology of spinal co
rd injury, in particular at the cervical level, requires further investigat
ion. In the present study, we used the extradural clip compression model in
the rat to examine the cellular distribution of apoptosis following cervic
al spinal cord injury, the relationship between glial apoptosis and post-tr
aumatic axonal degeneration and the possible role of apo[apoptosis]-1, CD95
(FAS) and p75 in initiating post-traumatic glial apoptosis. In situ termin
al-deoxy-transferase mediated dUTP nick end labeling revealed apoptotic cel
ls, largely oligodendrocytes as identified by cell specific markers. in gre
y and white matter following spinal cord injury. Apoptotic cell death was c
onfirmed using electron microscopy and by the demonstration of DNA ladderin
g on agarose gel electrophoresis. P-Amyloid precursor protein was used as a
molecular marker of axonal degeneration on western blots and immunohistoch
emistry. Degeneration of axons was temporally and spatially co-localized wi
th glial apoptosis. FAS and p75 protein expression was seen in astrocytes,
oligodendrocytes and microglia, and was also seen in some apoptotic glia af
ter cord injury. Both FAS and p75 increased in expression in a temporal cou
rse, which mirrored the development of cellular apoptosis. The downstream c
aspases 3 and 8, which are linked to FAS and p75, demonstrated activation a
t times of maximal apoptosis, while FLIP-L an inhibitor of caspase 8. decre
ased at times of maximal apoptosis.
We conclude that axonal degeneration after traumatic spinal cord injury is
associated with glial, in particular oligo dendroglial, apoptosis. Activati
on of the FAS and p75 death receptor pathways may be involved in initiating
this process. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights
reserved.