Stab wounds to rat brains: Demyelination, remyelination and the cellular response, particularly of oligodendrocytes

The present body of knowledge concerning the results of central nervous system injury is incomplete and controversial. The role of oligodendrocytes, the cells involved in phagocytosis, the stages of demyelination, and the evidence for remyelination are of interest. Following stab wounds to rat brain cortex, corpus callosum and hippocampus, the animals were examined at 4, 7, 11, 18, 23, 29, 45, 60 and 70 days postoperation (dpo). To help in the identification of cells immunocytochemical markers for astrocytes and immature oligodendrocytes were used. These were labels for glial fibrillary acidic protein (GFAP) and myelin/oligodendrocyte specific protein (MOSP) respectively. Light and electron microscopy were correlated using conventionally prepared and immunostained tissue. Immunocytochemistry for MOSP with light microscopy showed severe demyelination occurred following the stab wounds. Electron micrographs suggested that separation of the myelin sheaths at the intraperiod line is caused by separation of paranodal loops. This is followed by loss of the intraperiod line and the appearance of intramyelin vesicles. Myelin fragments formed and were phagocytosed by hematogenous macrophages, microglia and oligodendrocytes. A double spacing pattern was formed in the myelin fragments within the cytoplasm of phagocytes. Reactive MOSP-positive (+) cells were observed along the wound in the cerebral cortex and corpus callosum. The greatest density of stained cells was seen in the hippocampus. At 28 dpo these reactive oligodendrocytes were most numerous. A sharp decrease in number was noted between 28 and 60 dpo. At the same time, no oligodendroglial reaction was shown on the contralateral side. In the serial sections, GFAP+ astrocytes were detected on both sides of the brain. These GFAP+ astrocytes were different from reactive MOSP+ oligodendrocytes in terms of cell shape, distribution and timing. With electron microscopy MOSP+ cells showed features typical of immature oligodendrocytes. Remyelination was detected in the damaged tissue. Thin or loose myelin sheaths around axons, growth filopodia and/or oligodendroglial somas were seen. Direct connections between the plasma membranes of the oligodendroglial processes and the outer layer of the myelin sheath were noted. In conclusion, oligodendrocytes are reactive cells which have phagocytic abilities, increase in number near wounds, and make myelin when stimulated.