title: Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.
abstract: OBJECTIVE
  Microglia are resident immunocompetent and phagocytic cells of central nervous system (CNS), which produce various cytokines and growth factors in response to injury and thereby regulate disease pathology. The purpose of this study is to investigate the effects of microglial transplantation on focal cerebral ischemia model in rat.
  
  
  METHODS
  Transient middle cerebral artery occlusion (MCAO) in rats was induced by the intraluminal filament technique. HMO6 cells, human microglial cell line, were transplanted intravenously at 48 hours after MCAO. Functional tests were performed and the infarct volume was measured at 7 and 14 days after MCAO. Migration and cell survival of transplanted microglial cells and host glial reaction in the brain were studied by immunohistochemistry. Gene expression of neurotrophic factors, cytokines and chemokines in transplanted cells and host rat glial cells was determined by laser capture microdissection (LCM) and quantitative real time-PCR.
  
  
  RESULTS
  HMO6 human microglial cells transplantation group demonstrated significant functional recovery compared with control group. At 7 and 14 days after MCAO, infarct volume was significantly reduced in the HMO group. In the HMO6 group, number of apoptotic cells was time-dependently reduced in the infarct core and penumbra. In addition, number of host rat microglia/macrophages and reactive astrocytes was significantly decreased at 7 and 14 days after MCAO in the penumbra. Gene expression of various neurotrophic factors (GDNF, BDNF, VEGF and BMP7) and anti-inflammatory cytokines (IL4 and IL5) was up-regulated in transplanted HMO6 cells of brain tissue compared with those in culture. The expression of GDNF and VEGF in astrocytes in penumbra was significantly up-regulated in the HMO6 group.
  
  
  CONCLUSIONS
  Our results indicate that transplantation of HMO6 human microglial cells reduces ischemic deficits and apoptotic events in stroke animals. The results were mediated by modulation of gliosis and neuroinflammation, and neuroprotection provided by neurotrophic factors of endogenous and transplanted cells-origin.
authors.affiliation: Department of Neurology, Shimane University School of Medicine, Izumo, Japan.
authors.forename: Dashdemberel
authors.initials: D
authors.lastname: Narantuya
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagai
authors.forename: Abdullah Md
authors.initials: AM
authors.lastname: Sheikh
authors.forename: Junichi
authors.initials: J
authors.lastname: Masuda
authors.forename: Shotai
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D042282:Microdissection; D017628:Microglia / Q000166:cytology*; D009414:Nerve Growth Factors / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts
chemical_list: D016207:Cytokines; D009414:Nerve Growth Factors; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium