Radiation-induced apoptosis in the neonatal and adult rat spinal cord

This study was designed to characterize radiation-induced apoptosis in the spinal cord of the neonatal and young adult rat. Spinal cords (C2-T2) of 1- , 2 and 10-week-old rats were irradiated with a single dose of 8, 18 or 22 Gy, Apoptosis was assessed histologically according to its specific morphol ogical features or by using the TUNEL assay. Cell proliferation was assesse d immunohistochemically using BrdU, Identities of cell types undergoing apo ptosis were assessed using immunohistochemistry or in situ hybridization us ing markers for neurons, glial progenitor cells, microglia, oligodendrocyte s and astrocytes, The time course of radiation-induced apoptosis in 1- or 2 -week-old rat spinal cord was similar to that in the young adult rat spinal cord. A peak response was observed at about 8 h after irradiation, and the apoptosis index returned to the levels in nonirradiated spinal cords at 24 h, The neonatal rat spinal cord demonstrated increased apoptosis compared to the adult, Values for total yield of apoptosis over 24 h induced by 8 Gy in the neonatal rat spinal cord were significantly greater than that in th e adult. Immunohistochemistry studies using Leu7, galactocerebroside, Rip a nd adenomatous polyposis coli tumor suppressor protein indicated that most apoptotic cells were cells of the oligodendroglial lineage regardless of th e age of the animal. No evidence of Gfap or factor VIII-related antigen pos itive apoptotic cells was observed, and there was a small number of apoptot ic microglial cells (lectin-Rca1 positive) in the neonatal and adult rat sp inal cord. In the neonatal but not adult rat spinal cord, about 10% of the apoptotic cells appeared to be neurons and were immunoreactive for synaptop hysin, Labeling indices (LI) for BrdU in nonirradiated 1- and 2-week-old ra t spinal cord were 20.0 and 16.3%, respectively, significantly greater than the LI of 1.0% in the 10-week-old rat spinal cord. At 8 h after a single d ose of 8 Gy, 13.4% of the apoptotic cells were BrdU-positive in 10-week-old rat spinal cord, whereas 62.4 and 44.1% of the apoptotic cells showed BrdU incorporation in 1- and 2-week-old rat spinal cord, respectively. Regardle ss of the age of the animal, the apoptosis indices in BrdU-positive cells w ere greater than those in BrdU-negative cells. We conclude that the neonata l spinal cord demonstrates a greater level of apoptosis after exposure to i onizing radiation than the young adult spinal cord. This increase in apopto sis may be associated in part with the greater percentage of proliferating cells in the neonatal spinal cord, which demonstrate a greater level of rad iation-induced apoptosis than nonproliferating cells. (C) 2000 by Radiation Research Society.