Oligodendrocyte reactions and cell proliferation markers in human demyelinating diseases

We have carried out immunocytochemical reactions using antibodies to markers of oligodendrocytes, astrocytes, microglia and proliferating cells (PCNA) in sections of human brain in a variety of demyelinating conditions and human immunodeficiency virus (HIV) infection. In the acute phases of demyelinating diseases we found marked reactive changes in oligodendrocytes with hyperplasia and an increased cytoplasmic reaction using antibodies to enzymes involved in myelin formation. Proliferative responses were implied by the hyperplasia and the common finding of clusters of two or three adjacent oligodendrocytes at sites of acute myelin damage. This was borne out by studies using the PCNA antibody which gave negative reactions in normal brain but positive reactions in acute demyelination. Double staining for PCNA and cell markers showed that cells that had entered the cell proliferation cycle were to be found among astrocytes, microglia/macrophages and oligodendrocytes. In chronic demyelinating conditions, numbers of oligodendrocytes were reduced and cells in the proliferative cycle were not present, suggesting that the reactive potential of oligodendrocytes or their precursors and their capacity to respond to demyelination is limited.