Depletion of endogenous oligodendrocyte progenitors rather than increased availability of survival factors is a likely explanation for enhanced survival of transplanted oligodendrocyte progenitors in X-irradiated compared tonormal CNS

Oligodendrocyte progenitors (OPs survive and migrate following transplantat ion into adult rat central nervous system (CNS) exposed to high levels of X -irradiation but fail to do so if they are transplanted into normal adult r at CNS. In the context of developing Of transplantation as a potential ther apy for repairing demyelinating diseases it is clearly of some importance t o understand what changes have occurred in X-irradiated CNS that permit Of survival. This study addressed two alternative hypotheses. Firstly, X-irrad iation causes an increase in the availability of Of survival factors, allow ing the CNS to support a greater number of progenitors. Secondly, X-irradia tion depletes the endogenous Of population thereby providing vacant niches that can be occupied by transplanted OPs. In situ hybridization was used to examine whether;X-irradiation causes an increase in mRNA expression of fiv e known OP survival factors, CNTF, IGF-I. PDGF-A, NT-3 and GGF-2. The Level s of expression of these factors at 4 and 10 days following exposure of the adult rat spinal cord to X-irradiation remain the same as the expression l evels in normal tissue. Using intravenous injection of horseradish peroxida se, no evidence was found of X-irradiation-induced change in blood-brain ba rrier permeability that might have exposed X-irradiated tissue to serum-der ived survival factors. However, in support of the second hypothesis, a prof ound X-irradiation-induced decrease in the number of OPs was noted. These d ata suggest that the increased survival of transplanted OPs in S-irradiated CNS is not a result of the increases in the availability of the Of surviva l factors examined in this study but rather the depletion of endogenous OPs creating 'space' for transplanted OPs to integrate into the host tissue.