title: Effects of myeloablation, peripheral chimerism, and whole-body irradiation on the entry of bone marrow-derived cells into the brain.
abstract: Understanding how bone marrow-derived cells (BMDCs) enter the central nervous system (CNS) is critical for the development of therapies for brain-related disorders using hematopoietic stem cells. We investigated the brain damages and blood-brain barrier (BBB) modification following  either whole-body irradiation or a myeloablative chemotherapy regimen in mice, and the capacity for these treatments to induce the entry of BMDCs into the CNS. Neither treatment had a lasting effect on brain integrity and both were equally efficient at achieving myeloablation. Injection of  bone marrow cells from green fluorescent protein (GFP) transgenic mice was able to completely repopulate the hematopoietic niche in the circulation and in hematopoietic organs (thymus and spleen). However, GFP(+) cells only entered the brain following whole-body irradiation. We conclude  that myeloablation, damages to the brain integrity, or the BBB and peripheral chimerism are not responsible for the entry of BMDCs into the CNS following irradiation.
authors.affiliation: Laboratory of Endocrinology and Genomics, CHUL Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, Québec, Canada.
authors.forename: Antoine
authors.initials: A
authors.lastname: Lampron
authors.forename: Martine
authors.initials: M
authors.lastname: Lessard
authors.forename: Serge
authors.initials: S
authors.lastname: Rivest
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000166:cytology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002066:Busulfan / Q000494:pharmacology; D002465:Cell Movement; D046528:Chimerism; D003520:Cyclophosphamide / Q000494:pharmacology; D005720:Gamma Rays; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology; D014916:Whole-Body Irradiation
chemical_list: D018906:Antineoplastic Agents, Alkylating; D049452:Green Fluorescent Proteins; D003520:Cyclophosphamide; D017493:Leukocyte Common Antigens; D002066:Busulfan