title: Long-term cognitive effects of human stem cell transplantation in the irradiated brain.
abstract: OBJECTIVE
  Radiotherapy remains a primary treatment modality for the majority of central nervous system tumors, but frequently leads to debilitating cognitive dysfunction. Given the absence of satisfactory solutions to this serious problem, we have used human stem cell therapies to ameliorate radiation-induced cognitive impairment. Here, past studies have been extended to determine whether engrafted cells provide even longer-term benefits to cognition.
  
  
  METHODS
  Athymic nude rats were cranially irradiated (10 Gy) and subjected to intrahippocampal transplantation surgery 2 days later. Human embryonic stem cells (hESC) or human neural stem cells (hNSC) were transplanted, and animals were subjected to cognitive testing on a novel place recognition task 8 months later.
  
  
  RESULTS
  Grafting of hNSC was found to provide long lasting cognitive benefits over an 8-month post-irradiation interval. At this protracted time, hNSC grafting improved behavioral performance on a novel place recognition task compared to irradiated animals not receiving stem cells. Engrafted hESC previously shown to be beneficial following a similar task, 1 and 4 months after irradiation, were not found to provide cognitive benefits at 8 months.
  
  
  CONCLUSIONS
  Our findings suggest that hNSC transplantation promotes the long-term recovery of the irradiated brain, where intrahippocampal stem cell grafting helps to preserve cognitive function.
authors.affiliation: Department of Radiation Oncology, University of California , Irvine, CA , USA.
authors.forename: Munjal M
authors.initials: MM
authors.lastname: Acharya
authors.forename: Vahan
authors.initials: V
authors.lastname: Martirosian
authors.forename: Lori-Ann
authors.initials: LA
authors.lastname: Christie
authors.forename: Charles L
authors.initials: CL
authors.lastname: Limoli
mesh_terms: D000818:Animals; D001921:Brain / Q000528:radiation effects*; D003071:Cognition / Q000528:radiation effects; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control; D053595:Embryonic Stem Cells / Q000166:cytology / Q000637:transplantation; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation; D009474:Neurons / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000628:therapy; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D011923:Rats, Nude; D033581:Stem Cell Transplantation
keywords: Human stem cells; cognition; hippocampus; radiation; transplantation