Proliferative and migratory activity of glial cells in the partially deafferented hippocampus

The proliferative response of the glial cell population of the adult rat hippocampus deafferented by unilateral lesion of the entorhinal cortex was studied using 3H-thymidine autoradiography. Two experimental paradigms were used, involving: (1) intraventricular 3H-thymidine injection at a number of post-lesion intervals with sacrifice six hours later and (2) intraventricular injection at 30 hours post-lesion with sacrifice at 6, 96, or 192 hours later. The first increase in the number of labeled glial cells was obtained at 20 hours post-lesion and was confined to areas of degenerating axons. By 30 hours a large and uniformly dense proliferative response was observed throughout the ipsilateral, and medial aspects of the contralateral, hippocampus encompassing both deafferented and intact regions. Cell division continued through 50 and 65 hours post-lesion particularly in directly deafferented regions, but diminished to control levels by 80 hours. Although oligodendroglia and astrocyte-like cells were sometimes found to have incorporated the label the most common proliferative element within the hippocampus corresponded to previous light microscopic descriptions of "microglial" cells. The experiments using thymidine injection given at the peak proliferative period followed by survival periods of varying lengths indicated that a progressive redistribution of labeled nuclei occurred resulting in an accumulation of labeled cells in the zones of deafferentation. Multiple division of cells within these areas as well as the migration of nuclei from non-deafferented regions was found to contribute to this effect. The possible involvement of glial proliferation with other morphological effects of deafferentation, including the sprouting response of intact afferents, is discussed.