title: Transplantation of Induced Pluripotent Stem Cells Alleviates Cerebral Inflammation and Neural Damage in Hemorrhagic Stroke.
abstract: BACKGROUND
  Little is known about the effects of induced pluripotent stem cell (iPSC) treatment on acute cerebral inflammation and injuries after intracerebral hemorrhage (ICH), though they have shown promising therapeutic potentials in ischemic stoke.
  
  
  METHODS
  An ICH model was established by stereotactic injection of collagenase VII into the left striatum of male Sprague-Dawley (SD) rats. Six hours later, ICH rats were randomly divided into two groups and received intracerebrally 10 μl of PBS with or without 1 × 10(6) of iPSCs. Subsequently, neural function of all ICH rats was assessed at days 1, 3, 7, 14, 28 and 42 after ICH. Inflammatory cells, cytokines and neural apoptosis in the rats' perihematomal regions, and brain water content were determined on day 2 or 3 post ICH. iPSC differentiation was determined on day 28 post ICH. Nissl(+) cells and glial fibrillary acidic protein (GFAP)(+) cells in the perihematoma and the survival rates of rats in two groups were determined on post-ICH day 42.
  
  
  RESULTS
  Compared with control animals, iPSCs treatment not only improved neurological function and survival rate, but also resulted in fewer intracephalic infiltrations of neutrophils and microglia, along with decreased interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α), and increased IL-10 in the perihematomal tissues of ICH rats. Furthermore, brain oedema formation, apoptosis, injured neurons and glial scar formation were decreased in iPSCs-transplanted rats.
  
  
  CONCLUSIONS
  Our findings indicate that iPSCs transplantation attenuate cerebral inflammatory reactions and neural injuries after ICH, and suggests that multiple mechanisms including inflammation modulation, neuroprotection and functional recovery might be involved simultaneously in the therapeutic benefit of iPSC treatment against hemorrhagic stroke.
authors.affiliation: Third Department of Neurology and Key Disciplines Laboratory of Clinical Medicine of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qin
authors.affiliation: Third Department of Neurology and Key Disciplines Laboratory of Clinical Medicine of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China.
authors.forename: Xun
authors.initials: X
authors.lastname: Ma
authors.affiliation: Third Department of Neurology and Key Disciplines Laboratory of Clinical Medicine of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Qi
authors.affiliation: Third Department of Neurology and Key Disciplines Laboratory of Clinical Medicine of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.affiliation: Third Department of Neurology and Key Disciplines Laboratory of Clinical Medicine of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chemical and Life Science Engineering, Institute for Engineering and Medicine, Virginia Commonwealth University, Richmond, VA 23284, United States of America.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA 02114, United States of America.
authors.forename: Qing Mei
authors.initials: QM
authors.lastname: Wang
authors.affiliation: Third Department of Neurology and Key Disciplines Laboratory of Clinical Medicine of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China.
authors.forename: Shilei
authors.initials: S
authors.lastname: Sun
authors.affiliation: Third Department of Neurology and Key Disciplines Laboratory of Clinical Medicine of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Third Department of Neurology and Key Disciplines Laboratory of Clinical Medicine of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Third Department of Neurology and Key Disciplines Laboratory of Clinical Medicine of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China.
authors.forename: Xinjing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Third Department of Neurology and Key Disciplines Laboratory of Clinical Medicine of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China.
authors.forename: Haiman
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P. R. China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Gong
authors.affiliation: Third Department of Neurology and Key Disciplines Laboratory of Clinical Medicine of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007378:Interleukins / Q000032:analysis / Q000276:immunology; D008297:Male; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000276:immunology / Q000473:pathology; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
chemical_list: D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha