title: Mesenchymal stem cells prevent hydrocephalus after severe intraventricular hemorrhage.
abstract: OBJECTIVE
  Severe intraventricular hemorrhage (IVH) in premature infants and the ensuing posthemorrhagic hydrocephalus cause significant mortality and neurological disabilities, and there are currently no effective therapies. This study determined whether intraventricular transplantation of human umbilical cord blood-derived mesenchymal stem cells prevents posthemorrhagic hydrocephalus development and attenuates brain damage after severe IVH in newborn rats.
  
  
  METHODS
  To induce severe IVH, 100 μL of blood was injected into each lateral ventricle of postnatal day 4 (P4) Sprague-Dawley rats. Human umbilical cord blood-derived mesenchymal stem cells or fibroblasts (1 × 10(5)) were transplanted intraventricularly under stereotaxic guidance at P6. Serial brain MRI and behavioral function tests, such as the negative geotaxis test and rotarod test, were performed. At P32, brain tissue and cerebrospinal fluid were obtained for histological and biochemical analyses.
  
  
  RESULTS
  Intraventricular transplantation of umbilical cord blood-derived mesenchymal stem cells, but not fibroblasts, prevented posthemorrhagic hydrocephalus development and significantly attenuated impairment on behavioral tests; the increased terminal deoxynycleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling-positive cells; increased expression of inflammatory cytokines, such as interleukin-1α, interleukin-1β, interleukin-6, and tumor necrosis factor-α; increased astrogliosis; and reduced corpus callosal thickness and myelin basic protein expression after inducing severe IVH.
  
  
  CONCLUSIONS
  Intraventricular transplantation of umbilical cord blood-derived mesenchymal stem cells significantly attenuated the posthemorrhagic hydrocephalus and brain injury after IVH. This neuroprotective mechanism appears to be mediated by the anti-inflammatory effects of these cells.
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Seoul 135-710, Korea.
authors.forename: So Yoon
authors.initials: SY
authors.lastname: Ahn
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Chang
authors.forename: Dong Kyung
authors.initials: DK
authors.lastname: Sung
authors.forename: Se In
authors.initials: SI
authors.lastname: Sung
authors.forename: Hye Soo
authors.initials: HS
authors.lastname: Yoo
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Won Il
authors.initials: WI
authors.lastname: Oh
authors.forename: Won Soon
authors.initials: WS
authors.lastname: Park
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000473:pathology / Q000601:surgery*; D005260:Female; D006801:Humans; D006849:Hydrocephalus / Q000473:pathology / Q000517:prevention & control*; D007231:Infant, Newborn; D020547:Lateral Ventricles / Q000473:pathology / Q000601:surgery*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index