CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo

摘要: Chemotherapy in cancer patients can be associated with serious short- and long-term adverse neurological effects, such as leukoencephalopathy cognitive impairment, even when therapy is delivered systemically. The underlying cellular basis for these effects poorly understood. We found that three mainstream chemotherapeutic agents – carmustine (BCNU), cisplatin, cytosine arabinoside (cytarabine), representing two DNA cross-linking an antimetabolite, respectively applied at clinically relevant exposure levels to cultured cells are more toxic the progenitor of CNS nondividing oligodendrocytes than they multiple cell lines. Enhancement death suppression division were seen vitro vivo. When administered systemically mice, increased decreased subventricular zone, dentate gyrus hippocampus corpus callosum CNS. In some cases, was reduced, increased, weeks after drug administration ended. Identifying neural populations risk during any treatment great importance developing means reducing neurotoxicity preserving quality life survivors. Thus, well providing possible explanations systemic chemotherapy, strong correlations between our vivo analyses indicate same approaches we used identify reported toxicities also provide rapid screens analyzing new therapies discovering achieving selective protection or targeted killing.