Glial DNA synthesis and cell proliferation in the lesioned frontal cortex of the rat

Proliferation of rat neuroglial cells was quantified following a lesion of the frontal cortex, with the rate of incorporation of intraventricularly administered [³H]thymidine ([³H]TdR) into cortical DNA serving as an index of glial proliferation. Incorporation of [³H]uridine into the corresponding RNA fractions did not serve this purpose. The intraventricular route of administration of thymidine greatly reduced the amount of [³H]TdR needed to label DNA relative to systemic injection. The rate of incorporation of [³H]TdR into DNA was linear for 75 min post-injection. Significantly more [³H]TdR was incorporated into DNA of the lesioned frontal cortex than that of the contralateral control cortex, during the first 4 days post-trauma. The majority of the acid-insoluble radioactivity (from [³H]TdR) was localized in the nuclear subcellular fraction of the cortex. Experiments indicated that the enhanced incorporation of [³H]TdR was not the result of altered metabolism or pool sizes of TdR in the lesioned cortex. Histological analysis indicated that there was a significant increase in the number of glial cells in the lesioned cortex by day 4 post-lesion, which corresponded to the increase in DNA synthetic activity. It was concluded that mechanical trauma to the frontal cortex of the rat results in an increase in the number of glial cells at and near the lesion which is accompanied by an increase in incorporation of [³H]TdR into cortical DNA. This method of measuring posttraumatic DNA synthesis has several advantages over autoradiography.