title: Neuroprotective effects of human umbilical cord-derived mesenchymal stromal cells combined with nimodipine against radiation-induced brain injury through inhibition of apoptosis.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSCs) possess the ability to repair brain injuries. Additionally, nimodipine is a neuroprotective agent that increases cerebral blood flow and may help with the homing of MSCs to the injury site. Here we investigate the effectiveness of a combined human umbilical cord-derived MSCs and nimodipine therapy in radiation-induced brain injury (RIBI).
  
  
  METHODS
  Female mice received whole brain irradiation (WBI) and were treated with saline, nimodipine, hUC-MSCs, or hUC-MSCs combined with nimodipine. Body weight was measured weekly. An open field test for locomotor activity and a step-down avoidance test for learning and memory function were conducted at week 4 and week 12 post-WBI. The histological damage was evaluated by hematoxylin and eosin staining and glial fibrillary acidic protein immunohistochemistry. Quantitative polymerase chain reaction and Western blotting were used to detect apoptosis-related mediators (p53, Bax and Bcl-2).
  
  
  RESULTS
  In mice receiving the hUC-MSCs or the combined treatment, their body weight recovered, their locomotor and cognitive ability improved, and the percentage of necrotic neurons and astrocytes was reduced. The combined therapy was significantly (P < 0.05) more effective than hUC-MSCs alone; these mice showed decreased expression of pro-apoptotic indicators (p53, Bax) and increased expression of an anti-apoptotic indicator (Bcl-2), which may protect brain cells.
  
  
  CONCLUSIONS
  We demonstrated that hUC-MSCs therapy helps recover body weight loss and behavior dysfunction in a mice model of RIBI. Moreover, the effectiveness of the combined hUC-MSCs and nimodipine therapy is due to apoptosis inhibition and enhancing homing of MSCs to the injured brain.
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China; Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Wang
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wu
authors.affiliation: No. 307 Hospital of the Chinese People's Liberation Army, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Ya-Ru
authors.initials: YR
authors.lastname: Qin
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China. Electronic address: litong0883@163.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China. Electronic address: dhf553@163.com.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Duan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D001930:Brain Injuries / Q000378:metabolism / Q000628:therapy*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism*; D009553:Nimodipine / Q000494:pharmacology*; D011832:Radiation Injuries / Q000473:pathology / Q000628:therapy*; D014470:Umbilical Cord / Q000166:cytology*; D055544:beta-Globins / Q000235:genetics / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D055544:beta-Globins; D009553:Nimodipine
keywords: apoptosis; mesenchymal stromal cells; nimodipine; radiation-induced brain injury