Apoptotic Cells Associated with Wallerian Degeneration After Experimental Spinal Cord Injury: A Possible Mechanism of Oligodendroglial Death

Abstract

We have investigated the temporal and spatial profiles of apoptotic cells in an experimental transection spinal cord injury by the terminal deoxynucleotidyl transferase-mediated biotin-16-2'-deoxyuridine-5'-triphosphate nick-end labeling (TUNEL) method. Twenty-four hours postinjury, a numerous TUNEL-positive cells appeared both rostrally and caudally to the transection site. Those positive cells, however, gradually diminished in number by several days postinjury. In contrast, other TUNEL-positive cells were found scattered within the white matter remote from the lesion by the third day postinjury. These cells were typically embedded in or among vacuolated fibers, where they were identified in close proximity to the vacuolated space enclosed by myelin basic protein (MBP)-positive structures confirmed by TUNEL-MBP double staining. Because of their linear arrangement, these TUNEL-positive cells were considered interfascicular oligodendrocytes, a fact that was confirmed by the finding that some TUNEL-positive cells were also stained with CCI, a cell marker for oligodendrocyte. Electron microscopic studies revealed that the cells expressing apoptotic morphology were invariably encased in a space formed by myelin splitting. Although the biological significance of apoptotic interfascicular oligodendrocytes in the process of wallerian degeneration is yet to be determined, the finding of such profiles localized within degenerating myelin structures suggests that; oligodendrocytes may be "trapped" within rapidly swollen and disintegrating myelin lamellae, which isolates and perhaps predisposes them to death.

Peroxisome proliferator-activated receptor-γ agonist rosiglitazone reduces secondary damage in experimental spinal cord injury

“…[29][30][31][32] Apoptotic death of oligodendrocytes has been observed along the longitudinal axis of the spinal cord, and this may be involved in prolonged demyelination and deterioration of sensorimotor function. 33 Interventions that target apoptosis may therefore be beneEcial for the prevention of secondary degeneration following traumatic SCI. Apoptosis initially occurs at the lesion centre 6 h after injury and lasts for several days.…”

“…The proapoptotic protein, Bax, plays an important role in developmental cell death and central nervous system injury. 33 In addition, the administration of the antiapoptotic protein Bcl-2 into injured spinal cord tissue has been shown to increase neuronal survival, suggesting that SCI-induced decreases in Bcl-2 contribute considerably to neuronal death. 34 Compared with sham-operated animals, Bax levels were increased, and Bcl-2 was decreased, in spinal cord tissue 24 h after SCI in the present study.…”

Post-traumatic moderate systemic hypothermia reduces TUNEL positive cells following spinal cord injury in rat

“…Following SCI, apoptosis appears in the vicinity of the area affected by mechanical contusion, and since the chronological course of cell death is controlled, delayed cell death in spinal white matter somewhat specifically affects oligodendrocytes. 33,34 Oligodendroglial apoptosis is known to be associated with upregulation of caspase-3 for signaling in apoptosis 35 as well as FAS and p75 expression, 36 and has been shown to be related to progression of white matter degeneration. 37 In other words, the decrease of apoptotic cell death by hypothermia may reduce myelin damage, and contribute to the recovery of neurologic function.…”

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

“…Early apoptosis of neural cells including neurons is followed by a delayed wave of predominantly oligodendroglial apoptosis in degenerating white matter tracts (5)(6)(7)(8)(9). Studies of apoptosis in white matter after dorsal cordotomy or after transection suggest that glial apoptosis occurs, at least in part, as a consequence of axonal degeneration (10,11). Several studies have implicated the apoptotic role of caspases in the injured spinal cord (12)(13)(14)(15)(16)(17)(18)(19)(20)(21).…”