Proliferative Potential of Human Astrocytes

Although a number of studies have demonstrated proliferation of nonneoplastic astrocytes in experimental animal models, the proliferative potential of human astrocytes has not been well defined. Using double-label immunohistochemistry, we identified proliferating cells with the proliferation marker MIB-1 and astrocytes with glial fibrillary acidic protein staining in human biopsy and autopsy tissue. MIB-1 labeling of astrocytes was monitored in a variety of conditions containing significant numbers of reactive astrocytes, including infections, arteriovenous malformations, demyelinating lesions, metastatic tumors, and long-standing gliosis. Twenty-nine of a total of 54 cases showed no evidence of astrocyte-specific MIB-1 labeling despite prominent reactive changes. An average proliferation rate of 0.9% was present in the remaining 25 cases. Labeling indices were highest in infectious conditions and acute demyelinating lesions. We also examined astrocyte proliferation in 5 cases of progressive multifocal leukoencephalopathy. Astrocytic labeling indices were notably elevated in these cases, with an average labeling index of 5.8%. We conclude that low, but appreciable, astrocytic proliferation may occur in nonneoplastic human astrocytes. These findings have implications for astrocyte function in the normal and disease states and for the diagnostic distinction between reactive lesions and low-grade astrocytic neoplasms.