Repair Capacity of Adult Rat Glial Progenitor Cells Determined by anin VitroClonogenic Assay afterin Vitroorin VivoFractionated Irradiation

Abstract

Demyelination is one of the pathological conditions identified as a late response of the central nervous system (CNS) to irradiation. We have proposed that radiation-induced depletion of glial stem cells, which are the source of myelinating cells in the CNS, would lead to a lack of replacement of senescent or otherwise damaged oligodendrocytes. This impaired process of cell renewal would result in a decline of oligodendrocytes, i.e. demyelination. In the present study the repair capacity of glial stem cells was investigated and compared with the repair capacity of the CNS in vivo using functional endpoints. For this purpose, glial stem cells, derived from the adult rat optic nerve, were subjected to fractionated irradiation in vivo and in vitro and their survival was quantified with an in vitro clonogenic assay. The data were analysed by three different methods, all based on the LQ-model (single dose survival curve; ‘β_RR’, ‘F_e-plot’). The resulting value of the β-parameter of adult glial stem cells is consistent with values obtained for functional endpoints after irradiation of the CNS in vivo. The α/β-ratio (4·9–7·3 Gy) of adult glial stem cells, however, is higher than the α/β-ratio (∼ 2 Gy) obtained for CNS in vivo and is closer to that of an acute responding tissue.