Presence and significance of CD-95 (Fas/APO1) expression after spinal cord injury

Abstract

<jats:p content-type="fine-print"><jats:italic>Object.</jats:italic> A glycoprotein, CD95 (Fas/APO1) is widely considered to be implicated in the development of apoptosis in a number of tissues. Based on the hypothesis that apoptosis is related to cell death after spinal cord injury (SCI), the authors studied the presence and distribution of CD95 (Fas/APO1)-positive cells in injured spinal cord tissue for the purpose of determining the significance of this protein during the early phases of SCI.</jats:p> <jats:p content-type="fine-print"><jats:italic>Methods.</jats:italic> The presence and distribution of cells showing positive immunostaining for CD95 (Fas/APO1) were studied 1, 4, 8, 24, 48, and 72 hours and 1, 2, and 4 weeks after induction of experimental SCI in rats. Studies were conducted using a monoclonal antibody to the CD95 (Fas/APO1) protein. Positivity for CD95 (Fas/APO1) was observed in apoptotic cells, mainly in the gray matter, 1 hour after trauma, and the number of immunostained cells increased for the first 8 hours, at which time the protein was expressed in both gray and white matter. From 24 to 72 hours postinjury, the number of immunostained cells decreased in the gray matter, but increased in the white matter. From then on, there were fewer CD95 (Fas/APO1)-positive cells, but some cells in the white matter still exhibited positive immunostaining 1 and 2 weeks after injury. At 4 weeks, there remained no CD95 (Fas/APO1)-positive cells in injured spinal cord.</jats:p> <jats:p content-type="fine-print"><jats:italic>Conclusions.</jats:italic> These findings indicate that CD95 (Fas/APO1) is expressed after SCI, suggesting a role for this protein in the development of apoptosis after trauma and the possibility of a new therapeutic approach to SCI based on blocking the CD95 (Fas/APO1) system.</jats:p>

Umbilical Cord Blood Stem Cell Mediated Downregulation of Fas Improves Functional Recovery of Rats after Spinal Cord Injury

“…Several studies have implicated the apoptotic role of caspases in the injured spinal cord (12)(13)(14)(15)(16)(17)(18)(19)(20)(21). An increase in the number of cells expressing Fas was observed within 72 hours of SCI (22). Fas expression, activation of caspases 3 and 8, and apoptosis occur in a temporally similar fashion after SCI (23).…”

Neutralization of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Reduces Spinal Cord Injury Damage in Mice

“…Both DR4 and DR5 are present in the CNS of mammalians (Dörr et al, 2002) and mediate the detrimental effects of TRAIL in brain ischemia (MartinVillalba et al, 1999) and in b-amyloid-dependent neurotoxicity (Cantarella et al, 2003). Although it has been shown that after SCI, expression of TNF, CD95, and CD95L is increased at the lesion site (Zurita et al, 2001;Xu et al, 1998;Li et al, 2000), the in vivo function of the receptors belonging to TNFR superfamily and the respective ligands in SCI is still controversial. Neutralization of TNF (Lee et al, 2000) and CD95L (Demjen et al, 2004) reduces the number of apoptotic cells after SCI.…”

Post-traumatic inflammation following spinal cord injury

“…16,26,66 Apoptotic cells were observed, mainly in the grey matter, 1 h after trauma with an increase for the first 8 h, at which time the cells were found both in the grey and white matter. 86 Interestingly, from 24 to 72 h postinjury, the number of apoptotic cells decreased in the grey matter, but increased in the white matter. 86 Apoptotic cells are greatest in number closest to the lesion epicentre and are spatially associated with degenerating axons.…”

“…86 Interestingly, from 24 to 72 h postinjury, the number of apoptotic cells decreased in the grey matter, but increased in the white matter. 86 Apoptotic cells are greatest in number closest to the lesion epicentre and are spatially associated with degenerating axons. 26 Following contusion SCI in rats, apoptosis of oligodendrocytes is maximal 8 days postinjury.…”

“…These receptors recruit and activate caspase-8 and caspase-10 through their intracellular death domains. 26,[84][85][86] Fas and p75 receptors are expressed on oligodendrocytes, 29 astrocytes, and microglia in the spinal cord following SCI. 26 NMDA receptor activation by EAA, such as glutamate, promotes delayed apoptotic neuronal and glial cell death.…”