title: Mesenchymal stem cell transplantation attenuates brain injury after neonatal stroke.
abstract: OBJECTIVE
  Brain injury caused by stroke is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. Mesenchymal stem cells (MSC) have been shown to improve outcome after neonatal hypoxic-ischemic brain injury mainly by secretion of growth factors stimulating repair processes. We investigated whether MSC treatment improves recovery after neonatal stroke and whether MSC overexpressing brain-derived neurotrophic factor (MSC-BDNF) further enhances recovery.
  
  
  METHODS
  We performed 1.5-hour transient middle cerebral artery occlusion in 10-day-old rats. Three days after reperfusion, pups with evidence of injury by diffusion-weighted MRI were treated intranasally with MSC, MSC-BDNF, or vehicle. To determine the effect of MSC treatment, brain damage, sensorimotor function, and cerebral cell proliferation were analyzed.
  
  
  RESULTS
  Intranasal delivery of MSC- and MSC-BDNF significantly reduced infarct size and gray matter loss in comparison with vehicle-treated rats without any significant difference between MSC- and MSC-BDNF-treatment. Treatment with MSC-BDNF significantly reduced white matter loss with no significant difference between MSC- and MSC-BDNF-treatment. Motor deficits were also improved by MSC treatment when compared with vehicle-treated rats. MSC-BDNF-treatment resulted in an additional significant improvement of motor deficits 14 days after middle cerebral artery occlusion, but there was no significant difference between MSC or MSC-BDNF 28 days after middle cerebral artery occlusion. Furthermore, treatment with either MSC or MSC-BDNF induced long-lasting cell proliferation in the ischemic hemisphere.
  
  
  CONCLUSIONS
  Intranasal administration of MSC after neonatal stroke is a promising therapy for treatment of neonatal stroke. In this experimental paradigm, MSC- and BNDF-hypersecreting MSC are equally effective in reducing ischemic brain damage.
authors.affiliation: Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands. c.vanvelthoven-2@umcutrecht.nl
authors.forename: Cindy T J
authors.initials: CT
authors.lastname: van Velthoven
authors.forename: R Ann
authors.initials: RA
authors.lastname: Sheldon
authors.forename: Annemieke
authors.initials: A
authors.lastname: Kavelaars
authors.forename: Nikita
authors.initials: N
authors.lastname: Derugin
authors.forename: Zinaida S
authors.initials: ZS
authors.lastname: Vexler
authors.forename: Hanneke L D M
authors.initials: HL
authors.lastname: Willemen
authors.forename: Mirjam
authors.initials: M
authors.lastname: Maas
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
authors.forename: Donna M
authors.initials: DM
authors.lastname: Ferriero
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000473:pathology / Q000628:therapy*
chemical_list: D019208:Brain-Derived Neurotrophic Factor
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