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 to normal CNS.
Oligodendrocyte progenitors (OPs) survive and migrate following transplantation 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 rat CNS. In the context of developing OP transplantation as a potential therapy for repairing demyelinating diseases it is clearly of some importance to understand what changes have occurred in X-irradiated CNS that permit OP survival. This study addressed two alternative hypotheses. Firstly, X-irradiation causes an increase in the availability of OP survival factors, allowing the CNS to support a greater number of progenitors. Secondly, X-irradiation depletes the endogenous OP 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 five known OP survival factors, CNTF, IGF-I, PDGF-A, NT-3 and GGF-2. The levels 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 levels in normal tissue. Using intravenous injection of horseradish peroxidase, no evidence was found of X-irradiation-induced change in blood-brain barrier permeability that might have exposed X-irradiated tissue to serum-derived survival factors. However, in support of the second hypothesis, a profound X-irradiation-induced decrease in the number of OPs was noted. These data suggest that the increased survival of transplanted OPs in X-irradiated CNS is not a result of the increases in the availability of the OP survival factors examined in this study but rather the depletion of endogenous OPs creating 'space' for transplanted OPs to integrate into the host tissue.
Hinks
G L
GL
Department of Clinical Veterinary Medicine, University of Cambridge, Cambridge, UK.
Chari
D M
DM
O'Leary
M T
MT
Zhao
C
C
Keirstead
H S
HS
Blakemore
W F
WF
Franklin
R J
RJ
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000528:radiation effects; D016380:Brain Tissue Transplantation; D002452:Cell Count; D002470:Cell Survival / Q000528:radiation effects; D002490:Central Nervous System / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D020934:Ciliary Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D005260:Female; D006085:Graft Survival / Q000528:radiation effects; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000528:radiation effects; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D020934:Ciliary Neurotrophic Factor; D006133:Growth Substances; D007334:Insulin-Like Growth Factor I; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D020933:Neurotrophin 3; D010982:Platelet-Derived Growth Factor; D011509:Proteoglycans; D012333:RNA, Messenger; D020796:Receptor, Platelet-Derived Growth Factor alpha; D000099216:Chondroitin Sulfate Proteoglycan 4; C490580:Nrg1 protein, rat; C075278:platelet-derived growth factor A