"Anoikis" of oligodendrocytes induced by Wallerian degeneration: ultrastructural observations.

Oligodendrocytes undergo apoptosis in the white matter tracts remote from the experimental cord injury, although its significance is not understood. Our ultrastructural study, however, enabled us to speculate on its neurobiological implications. The spinal cords of male Wistar rats (4 week-old) were transected at Th11 level. At 4, 5, and 7 days after surgery the animals were transcardially perfusion-fixed. The removed cord was embedded in epoxy resin and examined by electron microscopy. Post-embedding terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) method was also performed. In the degenerative dorsal column above the transection, profiles of apoptotic oligodendrocytes were always found, embedded in a space formed by dilated degenerative myelin lamellae. Often, the dilated space in the myelin sheath lacked any apparent background proteinaceous matrix. In the electron microscopic TUNEL method, these apoptotic cells were electron dense in accordance with nuclear heterochromatinization. In conclusion, in the process of Wallerian degeneration, we observed the apoptosis of oligodendrocytes in a space formed by the split myelin sheath. These degenerative cells, which were enclosed in an ultrafiltrate-filled space formed by split myelin lamellae, were reminiscent of "anoikis."

Ischemic tolerance in chemical preconditioning: possible role of astrocytic glutamine synthetase buffering glutamate-mediated neurotoxicity.

Glutamine synthetase (GS), localized to astrocyte is a key enzyme in the glutamate-glutamine pathway in the brain. 3-Nitropropionic acid (3-NPA) is an irreversible inhibitor of succinate dehydrogenase in the tricarboxylic-acid cycle, and provides ischemic tolerance to the brain. So far, there have been no reports on the relationship of astrocytic GS and ischemic tolerance by chemical preconditioning. In order to test the hypothesis that astrocytes serve a pivotal role in 3-NPA-induced chemical preconditioning, we have investigated the temporal profile of GS expression in astrocyte parallel with those of glial fibrillary acidic protein and heat-shock protein 70 (HSP70). In our rat model of permanent focal ischemia, preconditioning with 3-NPA singnificantly reduced the subsequent neurological deficits and infarct volume within 24-72 hours after treatment. Immunohistochemically, protoplasmic astrocytes in the cortex and striatum were activated in terms of upregulation of GS and more abundant protoplasmic processes with 3-NPA preconditioning, however, HSP70 expression could not be induced. Thus, the activation of astrocytes and upregulation of GS play an important role in 3-NPA-induced preconditioning but HSP70 does not. In view of glutamate being imposed on the cerebral ischemic damage, the astrocytic GS may contribute to 3-NPA-induced ischemic tolerance.