Trauma‐induced proliferation of astrocytes in the brains of young and aged rats

Abstract

The time-course and magnitude of astrocyte proliferation following neural trauma was evaluated in young adult (3 months) and mid-aged (16-19 months) male Fischer 344 rats. One to 4 days after a needle wound was made through the cortex and the hippocampus, rats received three intraperitoneal injections of 3H-thymidine at 8 hour intervals and were sacrificed 1 hour after the last injection. For astrocyte quantification, 3H-thymidine autoradiography was combined with immunohistochemical staining for glial fibrillary acidic protein followed by semithin sectioning. In areas of the cortex and hippocampus adjacent to the wound, astrocytes were categorized as unlabeled or labeled with silver grains over the nuclei. Labeling index and numerical density of astrocytes were determined using stereological methods. The results showed that in both young and older rats, astrocyte proliferation is an early glial response to neural trauma, occurring during the first 4 postlesion days and contributing to an increase in astrocyte population. Regional differences in labeling index and numerical density suggest heterogeneity in the proliferative capacity of astrocyte subpopulations in the rat brain. Compared with young animals, older rats demonstrated greater labeling in the cortex but not in the hippocampus. Thus, aging is associated with region-specific increase in astrocyte reactivity to trauma possibly due to increased availability of mitogens or enhanced sensitivity of astrocytes to mitogenic signals.