title: Human neural stem cell transplantation ameliorates radiation-induced cognitive dysfunction.
abstract: Cranial radiotherapy induces progressive and debilitating declines in cognition that may, in part, be caused by the depletion of neural stem cells. The potential of using stem cell replacement as a strategy to combat radiation-induced cognitive decline was addressed by irradiating athymic nude rats followed 2 days later by intrahippocampal transplantation with human neural stem cells (hNSC). Measures of cognitive performance, hNSC survival, and phenotypic fate were assessed at 1 and 4 months after irradiation. Irradiated animals engrafted with hNSCs showed significantly less decline in cognitive function than irradiated, sham-engrafted animals and acted indistinguishably from unirradiated controls. Unbiased stereology revealed that 23% and 12% of the engrafted cells survived 1 and 4 months after transplantation, respectively. Engrafted cells migrated extensively, differentiated along glial and neuronal lineages, and expressed the activity-regulated cytoskeleton-associated protein (Arc), suggesting their capability to functionally integrate into the hippocampus. These data show that hNSCs afford a promising strategy for functionally restoring cognition in irradiated animals.
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Munjal M
authors.initials: MM
authors.lastname: Acharya
authors.forename: Lori-Ann
authors.initials: LA
authors.lastname: Christie
authors.forename: Mary L
authors.initials: ML
authors.lastname: Lan
authors.forename: Erich
authors.initials: E
authors.lastname: Giedzinski
authors.forename: John R
authors.initials: JR
authors.lastname: Fike
authors.forename: Susanna
authors.initials: S
authors.lastname: Rosi
authors.forename: Charles L
authors.initials: CL
authors.lastname: Limoli
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism / Q000601:surgery*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000601:surgery; D006801:Humans; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism / Q000601:surgery*; D051381:Rats; D011923:Rats, Nude
chemical_list: D003598:Cytoskeletal Proteins